OBJECTIVE： To investigate the preventive effect of Gynostemma pentaphyllum water extract on model rats with stress-induced gastric ulcer. METHODS： 60 rats were randomly divided into normal group， model group， positive group （Sanjiu weitai granules， 3.69 g/kg） and G. pentaphyllum water extract high-dose， medium-dose， low-dose groups （4.0， 2.0， 1.0 g/kg， calculated by crude drug）， 10 in each group. All rats were intragastrically administrated， once a day， for one week. After 2 h of administration， except for normal group， rats were induced to stress gastric ulcer model by water immersion method in other groups. After 3 h of modeling， ulcer index （UI）， ulcer inhibition rate were detected； superoxide dismutase （SOD） and malondialdehyde （MDA） in serum， tumor necrosis factor-α （TNF-α）， prostaglandin E2 （PGE2）， nitric oxide （NO） and endothelin-1 （ET-1） levels in gastric mucosal tissue were determined. RESULTS： Compared with normal group， SOD level in model group was decreased， while MDA level was increased in serum （P＜0.05）； PGE2， NO levels were decreased， TNF-α， ET-1 levels were increased in gastric mucosal tissue （P＜0.05）. Compared with model group， UI in administration groups were obviously decreased， above-mentioned indexes were obviously improved， which showed certain dose-dependence. And the levels of PEG2， ET-1 of gastric mucosal tissue in G. pentaphyllum water extract high-dose group improved more obviously than positive group， with statistical significances （P＜0.05）. CONCLUSIONS： G. pentaphyllum water extract plays a role in preventing gastric ulcer by regulating serum SOD-MDA balance， gastric mucosal tissue NO-ET-1 balance and reduce the degree of gastric mucosa injury， etc.