Objective: This study was devised to investigate the effects of prostaglandin E2 and diltizem on stress ulcer in rats.Methods: Twenty-one rats were used in the study. The effects of immobilization stress was examined at the stomach and jejunum, after surgical removal. The ulcer index, total acid, pH and mast cell counts were done. The first group was stressed without premedication to serve as the control. The second group received diltizem (Diltiazem 0.25 mg/Kg) and the third group received prostaglandin E2 (Dinoproston 50 microgram/Kg) before stress.Resuits: The diltizem and the PGE2 pretreated groups both had significantly lower mean ulcer indexes compared to the control group (p<0.001). Similarly the total acid of the diltizem and the PGE2 pretreated groups were lower (p<0.001, p<0.001). The pH of the diltizem and the PGE2 pretreated groups were higher (p<0.001, p<0.001) and the rise in the PGE2 group was more pronounced than the diltizem group (p<0.001). Mast cells were observed in the diltizem and PGE2 groups but not in the control group.Conclusion: PGE2 and diltizem was found to provide protection to the gastric mucosa against the erosive complications of stress and furthermore PGE2 was more effective than diltizem.