The effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion (I-R) injury was studied in rats. I-R injury was produced in rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 60 min. The increase in total area of erosions in the stomach after I-R and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by intragastric administration of sofalcone. In addition, sofalcone significantly inhibited the lipid-soluble free radical initiator-induced increase in lipid peroxides of the gastric mucosal homogenate, and could show scavenging action of superoxide radicals in aprotic solvent. These results showed that the protective effect of sofalcone against I-R-induced gastric mucosal injury is attributable to its antioxidant activities in the lipophilic phase.