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Pancreatic-derived proteases play a central role in the pathogenesis of ischemic intestinal injury. We postulated that exocrine bloekade by pretreatment with a Iong-acting somatostatin analogue, octreotide actetate, would attenuate isehemic mucosal injury. Sprague-Dawley rats received subcutaneous octreotide ( 10 (micro)g/kg/d) for 6 days by means of surgically implanted infusion ports. In a group of sham control rats, splanclmic blood flow (portal vein Doppler measurement ) and duodenal trypsin activity (p-toluene sulfonyl-L-arginine methyl ester assay) were determined. In a separate experiment, pretreated animals were subjected to 60 minutes of superior mesenterie artery ischemia alone or followed by 30 minutes of reperfusion. Gross extent of hemorrhagic necrosis and mieroseopic injury (rank analysis) were assessed by a blinded observer. Pretreatment with oetreotide reduced intraluminal duodenal trypsin activity by 46% without affecting portal blood flow. However, octreotide pretreatment significantly attenuated the microscopic depth of injury during isehemia and the extent of gross injury during reperfusion. It appears that somatostarill may have an adjuvant role in the prevention or progression of intestinal isehemic injury.