Background: Oxidative stress is observed in gastric ulceras it contributes to the mucosal injury. Melatonin (Mel) has protective functions of the gastric mucosa. Theaim of this study is to examine the protective effect of Melon gastric mucosa in acute lesions induced by hydrogen peroxide (H2O2) induced gastric lesions in rat model of ethanol-induced gastric ulcer. Methodology: This study was performed in male Sprague-Dawley rats (200–250 g) in 9 groups of equal size (n = 45): Intra-peritoneal (i.p.) injection of Mel (12.5, 25 and 50 mg/Kg) 30 min before H2O2treatment. Gastric ulcers were scored and ulcer index was calculated. Glutathione (GSH) and glutathione peroxidase (GSH-px) activity was measured using spectrophotometry. Gastric thiobarbituric acid reactive substance (TBARS) as an index of lipid peroxidation (LPO) was measured. Results: Gastric mucosal level of reduced glutathione (GSH) and glutathione peroxidase (GSH-px) activity were significantlydecreased by H2O2 administration, while melatonin pretreatment significantly increased both TBARS was increased after H2O2 administration and this increase was inhibited by melatonin. Melatonin was more protective, when compared with ranitidine and omeprazole. Mel gastro-protective effect was reduced by indomethacin and completely blocked by diethylmaleate. Conclusions: the results suggest that melatonin protects rat gastric mucosa against H2O2-induced damage possibly by scavenging reactive oxygen species via increases of GSH level, GSH-px activity and reduction of lipid peroxidation in the gastric mucosa. This suggests that Melmayprotect against alcohol induced peptic ulcer.