Acute pancreatitis (AP) is a common non-bacterial disease compromising pancreatic tissues. Adipocyte-derived leptin is closely associated with the severity and clinical outcome of pancreatitis. The potential protective effects of exogenous leptin administration on a rat model of severe AP (SAP) remain to be elucidated, and were examined in the present study. Male Wistar rats were divided into a sham operation group (SO), SAP model group (SAP) and leptin group (LEP). Each group was divided into three sub-groups by observation time (24, 48 and 72 h). The SAP models were prepared by retrograde injection of 6% sodium taurocholate into the pancreatic-bile duct. Following model establishment, exogenous leptin was intraperitoneally injected into mice at 50 mg/kg in the LEP group. Subsequently, serum amylase, lipase and glucose levels at particular time-points were analyzed using a fully-automatic biochemical analyzer, and serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were detected using an enzyme-linked immunosorbent assay. The pathological changes in pancreatic tissues were observed using hematoxylin and eosin staining, and the pancreatic expression of the long form of the leptin receptor (OB-Rb) was detected and evaluated using Nest-polymerase chain reaction analysis. The mortality rates of the model rats were compared between the groups. Following the administration of exogenous leptin, the serum level of amylase in the LEP group was significantly decreased at 48 h, compared with that in the SAP group, with serum lipase levels decreased at 48 and 72 h, and blood glucose levels decreased at 72 h. Regarding the serum inflammatory factors, the level of TNF-alpha in the LEP group was significantly lower, compared with that in the SAP group at 24 h; whereas no significant difference was observed in the serum level of IL-10 between the two groups. Regarding the pathological changes in the pancreas, the tissues in the LEP group showed significantly alleviated pancreatic inflammation. In addition, the pancreatic expression of OB-Rb in the LEP group was significantly higher, compared with that in the SAP group at 24 and 48 h. No significant difference in 3-day mortality rates were observed between the SAP group and the LEP group. Taken together, exogenous leptin administration regulated inflammatory factors and the expression of OB-Rb at the early stage of AP, which exerted protective effects by through the immunological and endocrinal pathways.