Objective To investigate the effect of leptin on transcription factor nuclear-κB (NF-κB) activity of pancreatic tissue and blood inflammatory cytokines (TNF-α,IL-1β) in severe acute pancreatitis. Methods Thirty-six rats were randomly divided into three groups, including sham group (group A, n = 12), AP model group(group B, n = 12) and Leptin treatment group (group C, n = 12). SAP was induced by intraductal injection of 5% sodium taurocholate into the pancreatic duct. Exogenous leptin was injected I. P. Fifteen minutes later. The concentration of serum amylase, leptin, TNF-α, IL-1βwere measured by radioimmunoassay 6 hours later. NF-κB activity of the pancreatic tissue were measured by immunohistochemistry. The changes of pathology of the pancreas were observed. Results The levels of serum amylase, cytokine TNF-αand IL-1βwere significantly reduced in group C, and the levels of serum leptin were significantly increased in group C. NF-κB activity in the pancreatic tissue in group B were significantly higher than that in group A. However, NF-κB activity of the pancreatic tissue in group C were significantly lower than that in group B. Furthermore, the extent of necrosis of the pancreatic tissue was re-lieved. Conclusion Exogenous leptin protected the rats pancreas against damage by sodium taurocholate. The protective effects of exoge-nous leptin were attributive to the reduction in cytokines TNF-α, IL-1β. The possible protective mechanism was that leptin decreased NF-κB activity.