Introduction Several previous studies have shown that obestatin exhibits protective and healing-promoting effects in some organs including the stomach, the kidneys, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis (CIP), and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration in the course of experimental acute ischemia/reperfusion (I/R) -induced pancreatitis in experimental models. Moreover, protective effect of pretreatment with obestatin in the cerulein-induced AP has been proved, however, no studies have investigated the consequences of this peptide administration on the course of cerulein-induced AP. Aim of the study The aim of the first series of the study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. The aim of the second series of the study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. The aim of the third series of studies was to determine the impact of obestatin therapy on the course of cerulein-induced pancreatitis. Methods In the first series of the study AP was induced by pancreat ; ic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16 nmol/kg/dose) was administered intraperitoneally twice: 0.5 h before exposure to ischemia, and 3 h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion and included histological, functional, and biochemical analyses. In the second series of the study AP was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. In the third series of the study AP was induced by cerulein given intraperitoneally 5 times with 1h intervals at the dose of 50 μg/kg/dose. Obestatin was administered twice a day at the dose of 8 nmol/kg/dose, starting with the first dose 24 h after the last injection of cerulein. Severity of acute pancreatitis was examined at 0 h or 1, 2, 3, 5, 7 and 10 days after the last injection of cerulein. Results and conclusions Administration of obestatin inhibited the development of ischemia/reperfusion-induced AP. This observation indicated that the protective effect of obestatin in the pancreas is universal and independent o ; f the primary cause of AP. Secondly, treatment with the exogenous obestatin reduced the severity of ischemia/reperfusion-induced AP and accelerated recovery of this disease. The involved mechanisms are likely multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin. Thirdly, treatment with exogenous obestatin reduced the severity of cerulein-induced AP and accelerated pancreatic recovery.