It is well known that ACTH/MSH-like peptides (melanocortins) apart from their classical endocrine effects exert pleiotropic non-endocrine actions. Heptapeptide Semax (MEHFPGP) is the analogue of ACTH(4–10) that has prolonged neurotropic activity in comparison to native peptide. Our previous data and clinic investigations have shown Semax analgesic activity. Furthermore we have shown earlier that Semax attenuates opioid form of stress-induced analgesia. The present work was carrying out in white rats. Pain sensitivity was measured by using Randall-Selitto paw-withdrawal test and tail flick test. Semax was administrated intraperitonealy at dose 0,5 mg/kg. Semax reduced pain threshold in paw-withdrawal test and had no effect in tail flick test. To study the mechanisms of Semax analgetic effects we used naloxone (opioid receptors antagonist) and morphine (mu-opioid receptor agonist). Intraperitoneal pre-treatment with naloxone (1mg/kg, 15 min before peptide injection) failed to influence Semax analgesic effect, naloxone 5 mg/kg reduced Semax analgesia in paw-withdrawal test. Semax administration 15 min before morphine (5 mg/kg) decrease morphine effects in paw-withdrawal test and have no influence in tail flick test. We can suppose that Semax effects on nociception depends on the level of opioid system activity.