L-lysine is an essential amino acid found in most protein food sources, in particular high-protein foods such as eggs, meat, soybean, milk and fish. This amino acid has been reported to have an indirect antioxidant property. Antioxidants are known to have gastroprotective property. This study examined the effect of L-lysine pre-treatment on indomethacin induced ulceration in male Wistar rats. Fifty male Wistar rats were used for this study and were randomly divided into two study groups of twenty five (25) animals each. The first subgroup was used for the anti-ulcer studies; antioxidant enzymes (SOD, CAT, and MDA), Nitric oxide, parietal cell count, and the mean ulcer score, while the second subgroup was used for the gastric mucus secretion study. Each subgroup was divided into five groups with five animals per group namely: Control, Omeprazole (20 mg/kg), L-lysine (100 mg/kg, 200 mg/kg and 400 mg/kg). The results showed that l-lysine pre-treatment significantly increased SOD activity and reduced MDA levels but with no significant change in catalase activity. NO levels in the treated groups were significantly higher than in the control. Gastric mucus secretion was significantly increased and the Original Research Article