Previous studies indicated that stress and glucocorticoids have modulatory effects on acute pain. The aim of present study was to determine the interaction between stress and glucocorticoids with activation of voltage dependent Ca2+ channel on modulation of acute pain in mice. Male albino mice (25-30 g) were used for this experiment. Tail flick and hot plate were used for evaluation of analgesic effect of the drug. We used subcutaneous injection of vehicle or dexamethasone (DEX) 30 min before or 1 min swimming stresses 5 min before observation period. Also, we used verapamil (10 mg, i.p.) as a voltage Ca2+ channel blocker 10 min before of DEX and stress. Results indicated that DEX and stress have analgesic effects as compared to control group and verapamil can significantly increase this effect (P<0.01). These findings provide further evidence for an important role of stress and glucocorticoids on modulation of pain and probably interaction with these effects and activation of voltage dependent Ca2+ channel.