Although acute gastric mucosal lesions (AGMLs) develop after the mucosal ischemia and reperfusion, precise intracellular mechanism for the development of AGMLs remains unclear. In the present paper, we investigated intracellular calcium level, lipid peroxidation, and gastric mucosal lesion in rat hemorrhagic shock model. We estimated intracellular calcium by measuring phosphorylase a activity in the gastric mucosa. The mucosal phosphorylase a increased during hemorrhagic shock, while it returned to be normal after the reinfusion of shed blood. Although mucosal lipid peroxide and area of AGMLs did not increase significantly during hemorrhagic shock, they increased significantly after the reinfusion. Diltiazem, a calcium antagonist, prohibited both of the increase in mucosal phosphorylase a activity during hemorrhagic shock and the increase in lipid peroxide content and area of AGMLs after the reinfusion of the shed blood. Organ reflectance spectrophotometry revealed that the gastric corpus suffered mucosal ischemia and hypoxia during the hemorrhagic shock. The are of AGMLs had a good correlation with a level of lipid peroxidation in the gastric mucosa. These results suggest 1) that intracellular free calcium in gastric mucosa increases during the mucosal ischemia; 2) that a calcium antagonist prohibits the increased intracellular free calcium during mucosal ischemia; and 3) that a calcium antagonist prohibits the increased mucosal lipid peroxide and the development of AGMLs after the mucosal reperfusion. Thus it is concluded that the increased intracellular free calcium during ischemia plays a key role in the mucosal tissue injury in the ischemia-reperfusion state.