To investigate the mechanism by which activated leukocytes induce gastric mucosal lesions, we examined whether granulocyte elastase is involved in the formation of such lesions in a rat model of hemorrhagic shock. Prospective, randomized, controlled study. Research laboratory at a university medical center. Male Wistar rats, weighing 220 to 280 g. Animals were subjected to hemorrhagic shock by phlebotomy. ONO-5046, a granulocyte elastase inhibitor (300 mg/kg ip), was administered 30 mins before or after phlebotomy. The effects of antithrombotic substances and tranexamic acid on hemorrhagic shock-induced gastric mucosal lesions also were examined. The effects of granulocyte elastase on the thrombomodulin activity and 35S-glycosaminoglycan content of endothelial cells were examined, using cultured human umbilical vein endothelial cells.