Objective: To investigate the effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference(CPP) in rats. Methods: The persistence,extinction and reinstatement of morphine-induced CPP were established.In clobenpropit group three different doses of clobenpropit (2,5 and 10 μg/rat,i.c.v.) were administered 15 min after morphine (1 mg/kg,i.p.) was injected.In histidine group histidine (100,200,500 mg/kg) was given 1 h prior to morphine treatment (1 mg/kg i.p). Results: The CPP was reinstated by priming injection of 1 mg/kg morphine.Clobenpropit (5,10 μg/rat) significantly inhabited the reinstatement by a priming dose of morphine-induced CPP compared with the morphine control group;histidine (100,200,500 mg/kg) significantly inhibited the reinstatement in a dose-dependent manner. Conclusion: Clobenpropit and histidine inhibit the revival of morphine-induced CPP in a dose dependent manner,indicating that endogenous histamine may inhibit relapse of morphine to some extent.