OBJECTIVE： To study the protective effects of Polygonum hydropiper extract on acute gastric mucosal lesion （AGML） in rats. METHODS： 48 rats were randomly divided into normal group （normal saline）， model group （normal saline）， positive group （ranitidine hydrochloride， 0.05 g/kg）， P. hydropiper extract low-dose， medium-dose and high-dose groups （2.7， 8.1， 24.3 g/kg by crude drug）， i.g. for consecutive 7 d， once a day. Except for normal group， other groups were given absolute ethyl alcohol to induce AGMI model after 1 h of last administration. 1.5 h after modeling， gastric mucosal lesion index of rats was calculated； the pathological changes of gastric tissue in rats were observed； nuclear factor E2 related factor 2 （Nrf2） content and SOD activity in gastric tissue of rats were determined by ELISA. RESULTS： Compared with normal group， the gastric mucosa of model group was damaged obviously， there was blood capillary rupture in submucosa， gastric mucosal lesion index was increased significantly（P＜0.01）； Nrf2 content and SOD activity were significantly decreased in gastric tissue of rats （P＜0.05 or P＜0.01）. Compared with model group， gastric mucosal lesion of rats was relieved to different extent； in positive group， P. hydropiper extract medium-dose and high-dose groups， gastric mucosal lesion index was decreased significantly （P＜0.05）， and Nrf2 content and SOD activity were increased significantly（P＜0.05 or P＜0.01）. CONCLUSIONS： P. hydropiper extract has good protective effect on absolute ethyl alcohol-induce AGMI， the mechanism of which may be associated with raising Nrf2 content and enhancing SOD activity in gastric mucosal tissue.