The study was designed to investigate the effect of oxytocin on the colonic smooth muscle contraction following chronic introgastric cool stress.Female SD rats were used and some of them were ovariectomized (OVX).A beading was inserted into colon in order to monitor the change of colonic transit in vivo.Longitudinal muscle strips of colon were prepared to monitored the contraction of colon in vitro.Plasma concentration ofoxytocin (OT)was detected by ELISA.OT receptor was investigated by Western blot analysis.Immunohistochemistry was used to locate OT receptor.Colon transit was longer in cool group (stomach irritation with cool physiological saline rats) than in normal group (stomach irritation with room temperature physiological saline rats).In cool group, the inhibitory effect of OT on proximal colonic muscle strips was enhanced.Tetrodotoxin (TTX) blocked the inhibitory effect of OT on colon.The concentration of oxytocin in blood was higher in cool group than in normal group.The expression of OT receptor protein in colon increased in cool group.The OT receptor located in myenteric plexus of colon in rats.The response of colonic muscle strips to OT was attenuated in OVX rats.These results suggested that OT enhances the inhibitory effect on proximal colonic contraction by binding with OT receptor of enteric plexus in stomach irritation with cool physiological saline rats.Estradiol is involved in the changes of colonic response to OT in intragastric administration with cold physiological saline rats.