This study examines the hypothesis that pentoxifylline protects renal PGE2 synthesis during mesenteric ischemia/reperfusion injury. Anesthetized Sprague-Dawley rats (300 g) were subjected to sham or superior mesenteric artery occlusion for 20 min followed by 30 min of reperfusion. The ischemia/reperfusion groups received either enteral allopurinol (10 mg/kg) daily for 5 d prior to ischemia, pentoxifylline (50 mg/kg) 10 min prior to ischemia or carrier. The kidney was removed and perfused in vitro with oxygenated Krebs buffer and the effluent was assayed for release of 6-keto-PGF1 alpha, PGE2 and thromboxane B2 (TXB2) by enzyme immunoassay. Mesenteric ischemia/reperfusion decreased renal PGE2 release by 50% (compared to sham) but did not alter release of TXB2 or 6-keto-PGF1 alpha. Pentoxifylline pretreatment (not allopurinol) preserved renal PGE2 release at the sham level. These data showed pentoxifylline exerted a protective effect against severe mesenteric ischemia/reperfusion injury by maintaining release of renal PGE2, a potent endogenous renal vasodilator.