In this study, the possible action of stress and glucocorticoids on the drug-seeking behavior was explored in the rats with morphine dependence. Forty rats were assigned into four groups randomly and received different treatments as follows: adrenalectomy; adrenalectomy + hydrocortisone 20 mg/kg S.C.; adrenalectomy + hydrocortisone 40 mg/kg S.C.; saline S.C.; The effect of adrenalectomy and hydrocortisone on morphine conditioned place preference (CPP) in rats with forced-swimming was observed. The results showed: 1. there was no significant difference for the adrenalectomized rats' spending time between the morphine and saline-paired side during the test session (t = 1.84, P > 0.05), but obvious differences of time spent between the morphine and saline-paired side were observed among the other three groups (P < 0.05 or P < 0.01); 2. the time spent in the morphine-paired side of the adrenalectomized group significantly decreased, compared with those of the other three groups, and there was no difference for the time spent in the morphine-paired side among the groups of adrenalectomy + hydrocortisone 20 mg/kg S.C., adrenalectomy + hydrocortisone 40 mg/kg S.C., and saline S.C.. These data suggested that adrenalectomy could decrease the facilitation action of morphine CPP induced by forced swimming in rats, whereas administration with glucocorticoids should reverse this effect.