A study was designed to compare the effect of omeprazole (orally) as a proton pump inhibitor and ranitidine (orally & i. m.) as H₂-receptor antagonist on stress-induced gastric ulcer in male albino rats (the mean ulcer score, and ulcer and preventive indices) and the effect of these drugs on gastric secretion (the mean volume of gastric juice, acid concentration, acid output and pepsin and mucous concentration). The incidence of ulceration was lowest in rats pretreated with omperazole and ranitidine in doses of 5.4 mg/kg b.wt (orally) and 10 mg/kg b.wt (i.m.) respectivily . Pretreatment of rats with omeprazole or ranitidine (the same dose) produced the lowest ulcer score and ulcer index and the highest preventive index. The mean volume of gastric contents (collected for 4 hrs.) was lowest in animals pretreated with a dose of 5.4 followed by 3.6 then 1.8 mg/kg b.wt omeprazole respectively. It was found that the greatest reduction of the mean acid concentration, acid output and pepsin concentration was evident with omeprazole in a dose dependent manner. It was found also that omeprazole significantly increases the mucus content of gastric secretion while ranitidine significantly decrease it.