Aim: to investigate the effect of L-citrulline and ranitidine (RAN) on indomethacin-induced gastric ulcer in male albino Wister rats. Methods: 50 male albino Wister rats were divided into 5 groups (10rats each): control received normal saline, indomethacin (IND) group; in which gastric ulceration was induced by a single dose of IND (30mg/kg) intragastrically, IND+RAN group; pretreated with RAN (50mg/kg) intragastrically, IND+ L-citrulline group; pretreated with L-citrulline (900mg/kg) intragastrically, IND+RAN+L-citrulline group; received co-treatment with RAN and L-citrulline intragastrically. At the end of experiments, ulcer index (U.I.) and preventive index (P.I.) and gastric juice pH, volume of gastric juice, free and total gastric acidity, pepsin activity and mucin content were assessed. Gastric homogenates were used for determination of Malondialdehyde (MDA), (nitrite/nitrate) NO content, prostaglandin E2 (PGE2), myeloperoxidase (MPO) activity and heme oxygenase (HO) activity. Results: pretreatment with either RAN or L-citrulline alone significantly reduced U.I. and also significantly reduced gastric juice volume, free and total acidity, pepsin activity, and gastric MDA with concomitant significant increase in pH of gastric juice. But, RAN insignificantly alter mucin content, NO content, PGE2, MPO activity and HO activity compared to IND group. While, pretreatment with L-citrulline alone significantly increased mucin content, NO content, PGE2, HO activity andsignificantly decreased MPO activity compared to either IND group or RAN group. Co-administration of RAN and L-citrulline resulted in more significant reduction of U.I. providing 87.30% prevention, and also more significant reduction of gastric juice volume, free and total acidity, pepsin activity, gastric MDA and MPO activity with concomitant more significant increase in pH of gastric juice and NO content, PGE2 synthesis and HO activity compared to either IND group or RAN groups. Conclusions: It could be concluded from this present study that the combination of L-citrulline and RAN afford a good gastroprotective potential against the gastric ulceration induced by IND better than each drug alone