The role of ischemia/reperfusion injury in pathogenesis of acute pancreatitis is still ill defined. It is accepted, however, that ischemia/reperfusion induces the development of post implantation pancreatitis that is responsible for considerable morbidity after pancreas transplantation. Preconditioning by brief exposure to ischemia protects the organ against damage evoked by subsequent severe ischemia. This study has been undertaken to check whether two brief ischemia periods protect the pancreas against severe ischemia/reperfusion induced pancreatitis. This study was performed on 30 male rats. Rats were divided into three groups (10 rats in each group). First group (control) underwent laparotomy without clamping of any artery. The second group underwent 30 min clamping of inferior splenic artery and then 1 hour reperfusion of pancreas and third group underwent clamping of inferior splenic artery (2×5 min with 5 min interval) as ischemic preconditioning and then 30 min clamping of inferior splenic artery and then 1 hour reperfusion of pancreas. Exposure to regular 30 min ischemia followed by 1 hr reperfusion led to the development of severe alteration more than other group that underwent ischemic preconditioning. Ischemic preconditioning, applied prior to induction of pancreatitis, caused the reduction in plasma lipase, plasma interleukin-1b and histological signs of pancreatic damage. We concluded that ischemic preconditioning of pancreas reduces the severity of ischemia/reperfusion induced pancreatitis. These effects are partly related to the release of proinflammatory factor interleukin -1b.