Abstract: Cyperus rotundus (CR) is widely used as a traditional folk medicine for treating various diseases such as gastrointestinal disorders, inflammatory and infectious diseases in Middle Eastern countries. However, the protective effects of CR extract on gastric mucosa has not been well defined. Thus, the aim of the present study was to investigate the protective effects of CR on gastric mucosal damage induced by ischemia and reperfusion in rats. Ischemia/reperfusion model was designed as of 30 min ischemia followed with 60 min reperfusion by clamping the celiac artery. The CR extracts were given at the doses of 100 or 200 mg kg-1 for preventing postischemic gastric mucosal injury. The study was carried out on equal five groups (n = 6) namely as follows: group I (sham, control group), group II (untreated ischemia control group), group III (treated ischemia group) was treated with 200 mg kg-1 CR, group IV (treated ischemia group) was treated with 100 mg kg-1 CR and group V (treated ischemia/reperfusion group) was treated with 200 mg kg-1 CR. Antioxidant enzymes activity such as Malondialdehyde (MDA) and glutathione-peroxidase (GSH-Px) were measured in the gastric tissue. Histopathological sections were examined for ischemic injury. The mean ulcer index of rats treated with 200 and 100 mg kg-1 CR were significantly lower (p<0.05) than that of control rats. The activities of GSH-Px and MDA were significantly affected (p<0.05) by treatment of CR in group III and group IV. These results indicate that both doses of CR extract have gastroprotective effect against acute gastric mucosal lesions induced by ischemia/reperfusion.