Semax (MEHFPGP) is the analogue of ACTH(4–10) that has prolonged neurotropic activity in comparison to native peptide. It was shown earlier that Semax effects behavioural and nociceptive changes induced by acute stress. In the present study we investigated the Semax effects on the changes of rat behavior induced by chronic stress. Rats were submitted to daily restraint stress (6 h/day) for 3 weeks. It was shown that the stress produced a decrease of body weight and an increase of adrenal weight. Furthermore 24 h after last restraint stressed animals showed increased anxiety-like behavior in elevated plus maze compared to unstressed ones. After termination of stress session the rats of stressed and unstressed groups were intranasally treated with Semax (0.05 mg/kg daily for 15 days) or vehicle. Animal behavior was recorded during period of peptide administration. It was shown that control stressed animals exhibited anxiety-like behavior in elevated plus maze and decreased exploration in the open field test compared to unstressed ones. Also stressed animals demonstrated increased immobility time in forced swim test. Therefore repeated restraint led to increase depression and anxiety level. Daily Semax administration significantly attenuated restraint stress-induced behavioral changes. Our data allow to suggest that Semax administration accelerate recovery of animal behavior after chronic stress.