Ischemia-reperfusion of the small intestine associated with hemorrhage and other shock states is characterized by increased microvascular permeability and mucosal barrier dysfunction. Glycoproteins play an important role as a barrier to diffusion, and some of the functions of prostaglandin E₁ (PGE₁) are related to mucosal protein synthesis. The present experiment was conducted to clarify the effect of PGE₁ on mucosal levels of glycoproteins and ATP following acute ischemia-reperfusion of the small intestine. The canine jejunum was isolated, and the blood flow was blocked for 30min with or without intravenous infusion of PGE₁. Mucosal levels of ATP, Na⁺-K⁺ ATPase activity, glucosamine, galactosamine, and cAMP decreased, and plasma endotoxin levels in portal blood increased, after reperfusion in the PGE₁-non-treated group. These changes were suppressed and mucosal levels of cAMP were increased by the administration of PGE₁. These results suggest that mucosal permeability increased and mucin synthesis decreased markedly following acute ischemia-reperfusion and that the administration of PGE₁ suppressed these changes by stimulation of ATP and cAMP synthesis. We also conclude that the administration of PGE₁ is useful to protect against acute ischemia-reperfusion injury in the small intestine.