1. It is known that inflammation influences peripheral and central mu-opioid receptor expression. Previous studies have indicated that glucocorticoids may influence the density of mu-opioid receptors. In the present study, we investigated the fluctuations of spinal mu-opioid receptor expression and hyperalgesia induced by complete Freund's adjuvant (CFA) under long-term administration of dexamethasone. 2. Adjuvant arthritis (AA) was induced by subcutaneous injection of CFA in the right hindpaw of male Wistar rats. Spinal mu-opioid receptor expression was detected by semiquantitative reverse transcription-polymerase chain reaction on Days 6 and 21 following AA induction. Dexamethasone (0.1 mg/kg) was administered intraperitoneally for 21 days. Variations in thermal hyperalgesia were checked by radiant heat on the same days as mu-opioid receptor expression was determined. 3. The results indicated a significant increase in spinal mu-opioid receptor expression on Days 6 and 21 after AA induction compared with the control group. Spinal mu-opioid receptor expression decreased significantly only on Day 21 in the AA + dexamethasone group compared with the AA alone group. Thermal hyperalgesia on Day 6 after AA induction showed a significant increase compared with the control group. Hyperalgesia decreased significantly on Day 21 after AA compared with Day 6. The AA + dexamethasone group showed a significant decrease in hyperalgesia on Day 6 compared with the AA group, but hyperalgesia increased significantly on Day 21 in the AA + dexamethasone group compared with the AA group. 4. The effects of long-term dexamethasone on both spinal mu-opioid receptor expression and hyperalgesia during persistent AA inflammation are time dependent. In addition, the effect of long-term dexamethasone administration on hyperalgesia during persistent arthritis inflammation needs to be investigated further.