Gastric ulcer is a common chronic disease in human digestive system. Massive alcohol drinking can lead to gastric ulcer. The gastroprotective effect and molecular mechanisms of Proanthocyanidin in a rat model of ethanol-induced gastric mucosal erosion were investigated. Thirty-five male rats were divided into five equal groups. Group 1 (Control normal): rats received no drugs. Group 2 (Early ulcer): rats received absolute ethanol (0.5 ml/100g) orally on empty stomach and sacrificed one hour later. Group 3 (Early ulcer + Proanthocyanidin protected): rats received proanthocyanidin orally at a dose of (300 mg/kg b. wt/day) for 3 weeks before ethanol administration then sacrificed after one hour. Group 4 (Late ulcer): rats received ethanol like group 2 and sacrificed after 21 days. Group 5 (Late ulcer + proanthocyanidin treated): rats first administered ethanol (0.5 ml/100g) and after one-hour proanthocyanidin was administered for 21 days. A significant increase in stomach L-MDA concentration with marked decrease in CAT activity and GSH concentration were observed in gastric erosion-induced rats. However, a significant depletion of gastric L-MDA level and marked increase in CAT activity and GSH concentration were observed after Proanthocyanidin treatment when compared to ulcerated rats. A significant up-regulation of gene expression level of BAX, NF-κB and IL-1β with downregulation of Bcl-2 gene were observed in stomach of gastric erosion-induced rats. However, a significant down regulation of BAX, NF-κB and IL-1β with up-regulation of Bcl-2 gene were observed after proanthocyanidin treatment. Conclusively, proanthocyanidin protects rat gastric mucosa against ethanol-induced gastric erosion via anti-inflammatory, anti-apoptotic and antioxidative mechanisms.