The majority of research on the endogenous opioid system has focused on various pain assays and the efficacy of different opioid agonists. However, minimal attention has been focused on the effects of gonadal hormones and their impact on the opioid peptide system. The present study was designed to determine the effects of modulation of gonadal hormones on the opioid receptor protein levels in Complete Freund's Adjuvant (CFA)-treated arthritic and non-arthritic male and female Lewis rats. Midbrain and spinal cord tissues were collected for comparison of the μ, δ, and κ receptor protein levels in arthritic and non-arthritic animals. Male gonadectomy did not dramatically impact opioid receptor protein levels, whereas female gonadectomy resulted in significant increases in opioid receptor protein levels. Furthermore, it was determined that MOR protein levels were greatest in male rats, while KOR protein levels were greatest in female rats regardless of arthritis condition or gonadal hormones.