Confidential

Exhibit 10.6

June 23, 2004

REVISED

James E. Barrett, PhD

31 Tweed Boulevard

Upper Grandview, New York 10960

Dear Dr. Barrett:

On behalf of Adolor Corporation (the “Company”), we would like to offer you the position of Chief Scientific Officer and President, Research, reporting directly to Dr. David Jackson, Sr. Vice President, Research and Development. This offer is contingent upon our receipt of employment and education references that meet our standards of acceptability as well as the completion of a satisfactory criminal background check in compliance with the Fair Credit Reporting Act.

In this position, you will receive a Base Salary of $27,375.00 per month, the equivalent of $328,500 on an annual basis, subject to the normal payroll withholding taxes in accordance with the Company’s customary practices. Adolor’s current pay practice is to make direct payroll deposits on alternate Fridays.

Benefits

As a full time employee, you will be eligible to participate in the Company’s employee benefit programs. Currently these benefits include:

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You should be aware that benefits are subject to change at the discretion of the Company.

Incentive Compensation

You will also be eligible to participate in the Company’s cash incentive compensation plan. Bonuses are discretionary, and are subject to the approval of the Board of Directors. Your annual bonus target will be 30% of your base salary based on your performance against individual objectives and the achievement of company milestones. You are not eligible for a bonus payment until after completion of 90 days of employment. As a new hire, your bonus payment may be pro-rated your first year based on your hire date. These bonus payments are currently paid out shortly following year-end and you must be employed by the company to receive any bonus.

Sign On Bonus

You will be eligible to receive a $50,000 sign on bonus. Twenty-Five Thousand Dollars ($25,000) will be provided to you following the first 30 days of employment and the remaining Twenty-Five Thousand Dollars ($25,000) will be provided to you at the end of 90 days of continuous employment. Both of these checks are subject to normal payroll taxes. If you should voluntarily resign your position with Adolor or are terminated for cause within one year of your start date, you are responsible to the company for full reimbursement of this sign-on bonus in the amount of $50,000.

Relocation

It is agreed that you will relocate from Upper Grandview, NY to the Suburban Philadelphia area. To assist you in the relocation of you and your family, Adolor Corporation is pleased to offer Relocation Benefits for Homeowners as outlined in the attached Relocation Assistance Policy.

Relocation benefits will include:

Applicable and approved expenses will be grossed-up for federal and state taxes.

Please contact Alex DiGiacomo, Human Resources Manager, with any questions and before initiating any aspect of the relocation process. We will coordinate an introduction between you and a consultant from Prudential Fox Roach, our corporate relocation assistance vendor.

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It is agreed that if you voluntarily leave Adolor, within twelve (12) months following your relocation, you will be required to reimburse the company for all expenses incurred for your relocation.

Annual Performance Review

Your individual performance will be evaluated during our annual review process. Currently, our annual review process takes place at the end of each calendar year, followed by the merit increase process in January. You will receive a review during our 2004 review cycle, which will include a review of your cash compensation and stock options. As a new hire, your merit increase may be pro-rated your first year based on your hire date.

Stock Option Program

Upon joining the Company, you will have the opportunity to participate in the Company’s stock option program. Subject to the approval of the Compensation Committee, you will be offered an option to purchase 100,000 shares of Adolor’s common stock. These options will be subject to the terms of the Adolor Corporation’s 2003 Stock-Based Incentive Compensation Plan (“Plan”). A copy of the Plan is attached for your reference. The options will be Incentive Stock Options to the maximum extent available under tax regulations and your right to purchase the stock (exercise a portion of the option) will vest in equal monthly amounts over a 48-month period commencing on your start date, subject to an initial three month waiting period.

At the time of the annual review, if your performance is satisfactory or better, you will be considered for additional discretionary option grants.

Termination of Employment

You will have the right to terminate your employment hereunder with or without Good Reason (as defined below), as provided below, and the Company will have the right to terminate your employment hereunder with or without Cause or (as defined below), as provided below. Except as provided for in the immediately following paragraph, if your employment hereunder is terminated at any time (i) by you for Good Reason following 15 days prior written notice to the Company, or (ii) by the Company without Cause, or if a Change in Control occurs and your employment hereunder is terminated at any time during the 90 days before or the first twelve months following such Change in Control (i) by you for Good Reason following 15 days prior written notice to the Company, or (ii) by the Company without Cause, you will be entitled to receive from the Company (a) in twelve monthly installments a payment in gross amount equal to the sum of (i) your Base Salary and (ii) the bonus amount paid to you for your performance during the immediately preceding calendar year, (b) continuation of similar benefits in effect as of the date of termination for a period of one year following the date of termination at the Company’s sole expense, (c) immediate payment of any unpaid expense reimbursements, deferred compensation and unused accrued vacation days through the date of termination, (d) the ability to exercise all equity interests in the Company that have vested up through the date of termination during the period of one year following the date of termination, and (e) any other payments and/or benefits which you are entitled to receive under the terms and provisions of any of the employee pension, incentive, or welfare benefit plans of the Company.

In the event your employment is terminated (i) by you voluntarily without Good Reason, or (ii) by the Company for Cause, you will only be entitled to receive from the Company (a) your Base Salary through the date of such termination, (b) immediate payment of any unpaid expense reimbursements, deferred compensation and unused accrued vacation days through the date of termination, and (c) any other payments and/or benefits which you are entitled to receive under the terms and provisions of any employee pension, incentive or welfare benefit plans of the Company.

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If your employment is terminated due to your death, your estate will be entitled to receive from the Company (a) Base Salary continuation through the end of the month in which your death occurs, (b) a pro-rated bonus payment for the year of death equal to the bonus amount paid to you for your performance during the immediately preceding calendar year multiplied by a fraction, the numerator of which is the number of days from and including January 1 of such year through the date of your death and the denominator of which is 365, (c) immediate payment of any unpaid expense reimbursements, deferred compensation and unused accrued vacation days through the date of death or such termination, and (d) any other payments and/or benefits which you are entitled to receive under the terms and provisions of any employee pension, incentive or welfare benefit plans of the Company.

In the event of any termination of your employment, you will be under no obligation to seek other employment and there will be no offset against any amounts due to you hereunder on account of any remuneration attributable to any subsequent employment that you may obtain. Any amounts due under “Termination of Employment” are in the nature of severance payments, or liquidated damages, or both, and are not in the nature of a penalty. Notwithstanding the foregoing, the Company’s obligation to provide continuation of benefits under the welfare benefit plans described above shall cease if you become eligible for other health insurance benefits at the expense of a new employer. You agree to notify a duly authorized officer of the Company, in writing, immediately upon acceptance of any employment following the date of termination of your employment which provides you with eligibility for health insurance benefit.

For purposes of the Agreement, “Cause” means (a) your conviction (including a plea of guilty or nolo contendere) of a felony under federal law or the law of the state in which such action occurred, (b) the commitment by you of an intentional act of fraud, embezzlement, or theft in connection with your duties in the course of your employment with the Company, or your engagement in gross negligence in the course of your employment with the Company or (c) your willful and deliberate failure to perform your employment duties in any material respect. For purposes of the Agreement, an act or omission on your part shall be deemed “intentional” or gross negligence only if it was done by you in bad faith, not merely an error in judgment, and without reasonable belief that the act or omission was in the best interest of the Company.

For purposes of the Agreement, “Good Reason” means and will be deemed to exist if, without your prior express written consent, (i) you are assigned any duties or responsibilities inconsistent in any respect with the scope of the duties or responsibilities associated with your title or position, as set forth and described above; (ii) you suffer a material change in the duties, responsibilities, reporting rights or obligations, or effective authority associated with your title and position and/or as set forth above; (iii) your Base Salary is decreased by the Company, or your benefits under any of the Company’s employee pension or welfare plans or programs are in aggregate materially decreased; or (iv) the Company fails to pay your compensation, employee benefits or reimbursements when due; provided that in the event of a Change in Control, “Good Reason” shall also include the relocation of your principal office location to a site that is more than 50 miles from your then current principal office.

For purposes of the Agreement, “Change in Control” means (A) the consummation of a merger or consolidation of the Company in which the stockholders of the Company immediately prior to such merger or consolidation, would not, immediately after the merger or consolidation, beneficially own (as such term is defined in Rule 13d-3 under the Securities Exchange Act of 1934, as amended), directly or indirectly, shares representing the aggregate 50% or more of the combined voting power of the securities of the corporation issuing cash or securities in the merger or consolidation (or of its ultimate parent corporation, if any); or (B) the stockholders of the Company approve a plan of complete liquidation or dissolution of the Company, or there is consummated an agreement for the

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sale or disposition by the Company of all or substantially all of the Company’s assets, other than a sale or disposition by the Company of all or substantially all of the Company’s assets to an entity, at least 50% of the combined voting power of the voting securities of which are owned by persons in substantially the same proportion as their ownership of the Company immediately prior to such sale.

Miscellaneous Items

You will receive a Company cell phone or Blackberry that is paid monthly by Adolor with the understanding that you comply with the Company Policy regarding its use.

Conditions of Employment

As a condition of employment with the company, which you understand to be at-will employment, we require that you sign the enclosed Employee Noncompetition, Nondisclosure and Development Agreement and return it to me. This offer will expire at 5:00 p.m. on Friday, June 25, 2004 unless you accept it prior to that time. If you wish to accept this offer based on the terms defined in this letter, please call me at ###-###-#### Please sign, date, and return the enclosed copy together with the signed Employee Noncompetition, Nondisclosure and Development Agreement in the envelope enclosed. Please do not fax either of these documents to Adolor.

Dr. Barrett, we sincerely hope that you will accept our offer and we are eager to have you join Adolor Corporation. We would anticipate, if you accept our offer, that your employment would begin on a mutually agreed upon date. We are looking forward to working with you and supporting you in your work so that your contributions lead the Company to even greater future success.

Please feel free to call me if you have any questions about this offer or any other aspect of Adolor.

Sincerely,

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