Microcirculatory derangements in the pancreas associated with acute pancreatitis may contribute to a low-flow state and lead to pancreatic necrosis. This study investigated the effects of glucagon, a selective mesenteric arterial dilator, on pancreatic ischemia in canine bile-trypsin-induced pancreatitis (BTP). Measurements of cardiac Index (CI), total pancreatic blood flow (QP), pancreatic oxygen consumption (O2CP), and pancreatic arteriovenous shunt flow (QAVS) were obtained prior to and after inducing BTP. Bile-trypsin-induced pancreatitis was induced in 18 dogs. Nine received lactated Ringer's solution alone (LRPAN) at 6.5 mL/kg/hr, nine received lactated Ringer's solution plus continuous Intravenous (IV) glucagon hydrochloride (GLUPAN) at 1.0 micrograms/kg/min, and nine undergoing periportal dissection without BTP received IV glucagon (GLUCON). Following BTP, CI, QP, and O2CP decreased significantly and QAVS remained unchanged in crystalloid-treated animals (LRPAN). Glucagon administration (GLUPAN) transiently increased CI and QP but failed to improve O2CP and did not change QAVS. The decrease in O2CP observed after BTP in association with a constant QAVS suggests a metabolic block to oxygen uptake at the cellular level. Glucagon in pharmacologic doses does not reverse abnormalities in O2CP and is therefore of questionable physiologic benefit in the treatment of acute pancreatitis.