Background: Ischemia-reperfusion (I/R) is a causative factor in the pathogenesis of acute pancreatitis. L-arginine plays a key role in the relationship between microcirculatory disorders and I/R injuries. Heme oxygenase- 1 (HO-1) has been identified as a stress protein induced in many cell types by various stimulants, such as oxidative stress. Aim: The present study aimed to investigate the effects of L-arginine on HO-1 in pancreatitis resulting from ischemia and reperfusion. Materials and Methods: Pancreatic arterial vessels were prepared and clamped for 1 hour, then released after 3 hours. Animals were divided into 5 groups, sham, L-arginine+ischemia without reperfusion, saline+ischemia without reperfusion, L-arginine+ischemia with reperfusion, and saline+ischemia with reperfusion. Blood was collected for amylase and myeloperoxidase (MPO) and pancreatic tissue was collected for superoxide dismutase (SOD), malondialdehyde (MDA), heme-oxygenase-1 (HO-1), and histopathologic grading of pancreatic injuries. Results: Levels of amylase, MPO, SOD, and MDA in the L-arginine+ischemia without reperfusion and L-arginine+I/R groups were lower than in saline+ischemia without reperfusion and saline+I/R groups (p<0.05). In the L-arginine+I/R group, these parameters were lower than the L-arginine+ischemia without reperfusion group (p<0.05). In the saline+ischemia without reperfusion group, MPO, SOD, and MDA levels were significantly higher, compared to the saline+I/R group (p< 0.05). HO-1 expression was significantly higher in the L-arginine treated groups. It was highest in the L-arginine+I/R group (p< 0.05). Histopathological findings also supported the protective roles of L-arginine. Conclusion: Present data suggests that L-arginine, inducing HO-1 expression, could be useful in preventing oxidative damage associated with I/R induced pancreatitis.