This study was performed for evaluation of the effect of pre-operative and post-operative administration of tramadol and meloxicam combination on hyperalgesia and selected inflammatory responses after sciatic nerve ligation in rats. An eighty male Wistar rats (Rattus norvegicus) were divided into two groups; preemptive analgesic group, in which the rats received analgesic agents 30 min before nerve ligation. Also the nociceptive pain tests were detected before surgery, 120 and 150 min post-analgesics injection. The serum IL-6 and PGE-2 concentrations were detected at 150 min post-analgesics injection. The second group was post-operative analgesic group; in which the rats exposed for the nerve ligation then the rats received analgesic agents at 5 till 11 day’s post-operative. Behavioral tests were performed before surgery and on each even days post-operatively. The serum concentration of IL-6 and PGE-2 was determined at 5, 10 and 14 days post-operative. Tramadol and meloxicam combination had a statistically significant (P < 0.05) reverse hyperalgesia while preemptive administration of tramadol and meloxicam significantly decreased (P < 0.05) serum IL-6 production compared to post-operative treatment. In conclusion, the preemptive combination of tramadol and meloxicam produced a potent analgesic effect post nerve ligation in rats