Previous studies indicated that glucocorticoids have modulatory effects on acute pain and probably one of the factors that mediate these effects is nitric oxide. The aim of this study was to determine interaction between corticosterone and Nitric oxide (NO) system on acute pain in Hot plate (HP) and Tail Flick (TF) models in mice. In this experimental study we used 140 male albino mice (25–30 gr) in 14 groups. Also we used of HP and TF tests for evaluation of acute pain. The criteria for evaluation of pain was measure of latency time that animal reaction to pain responses that include of: elevate of tail in TF and liking of paw in HP. All animals received two IP injections, L-Name (10 mg/kg) as a NO synthesis inhibitor or L-Argininie (20 mg/kg), as a NO precursor 60 min and different doses of corticosterone (1and 3 mg/kg) or Vehicle (Propylene glycol 40% + Saline in 6 ml) were injected 30 min before of evaluation test. Analysis of data indicated that corticosterone at doses of 1 and 3 mg significantly reduced acute pain reaction in mice. Also pre-treatment of LA inhibits the analgesic effects of corticosterone in both tests, while injection of LN had no significant effects. The findings above have shown that glucocorticoids induced analgesic effects probably through modulation of NO system.