Gastric ulcer is a common chronic disease in human digestive system. Excessive alcohol drinking can lead to gastric ulcer. The gastroprotective effect and molecular mechanisms of probiotics in a rat model of ethanol-induced gastric injury were evaluated. Thirty five rats divided into five equal groups. Group 1 :( Control normal) rats received no drugs. Group 2 :(Early ulcer) rats received absolute ethanol (0.5ml/100g rat) orally on empty stomach and sacrificed one hour later. Group 3 :( Early ulcer + Probiotics protected) rats received probiotic orally (135 mg/kg b.wt/day) for 3 weeks before ethanol administration then sacrificed after one hour. Group 4: (Late ulcer) rats received ethanol similar to group 2 and sacrificed after 21 days. Group 5: (Late ulcer + Probiotics treated) rats first administered with ethanol and after one hour probiotic was administered for 21 days. A significant increase in L-MDA with marked decrease in GSH and CAT were shown in stomach of gastric injury-induced in rats compared with control group. Conversely, a significant decrease in L-MDA and obvious increase in GSH and CAT were observed after probiotics treatment compared to ulcerated rats. Likewise, a significant up-regulation of NF-κB gene expression level was observed in stomach of gastric injury-induced in rats. This expression was downregulated after probiotics administration. Meanwhile, a significant down-regulation of PPARγ and TGF-β1 gene were detected in gastric injury-induced rats. This expression was upregulated after probiotics administration. Conclusively, probiotics improving gastric cell proliferation and protect gastric mucosa against injury-induced in rats via anti-inflammatory and anti-oxidative mechanisms.