Objective:To evaluate the protective effect of Shenfu injection (SFI) against intestinal barrier dysfunction and second hit in rats with severe acute pancreatitis (SAP).Methods:Fifty-four male Wistar rats were randomly divided into sham operation group (n=6),SAP group (n=24),and SAP+SFI group (10 ml/kg body wt,n=24).Sham operation group underwent laparotomy only.SAP model was established by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct of Wistar rats.SAP+SFI group was given SFI (10 ml/kg) intaperitoneally 2 h before SAP establishment.Rats were sacrificed at 3,6,12 and 24 hours after operation.The samples of pancreas,lung and liver were collected for measuring the levels of myeloperoxidase (MPO) at 3,6,12,and 24 h after injection of sodium taurocholate.The pathological changes of the terminal ilea were observed under light microscopy,and the blood levels of diamine oxidase (DAO),tumor necrosis factor alpha (TNF-α) and interleukin-6(IL-6) were also measured at different time points.Results:The blood levels of TNF-α,IL-6 and DAO in SAP group were significantly higher than those in the sham operation group at all time points (P<0.01).The levels of intrapulmonary,intrapancreatic and intrahepatic MPO in SAP group were significantly than those in the sham operation group at 6,12,and 24 hours (P<0.01).The contents of DAO,TNF-α and IL-6 were significantly decreased in SAP+SFI group compared with in SAP group at all time points(P<0.05 or P<0.01).The contents of intrapulmonary,intrapancreatic and intrahepatic MPO were significantly decreased in SAP+SFI group compared with SAP group at 6,12, and 24 h after operation(P<0.05 or P<0.01).Intestinal pathological damages were obviously milder in SAP+SFI group than that in SAP group at 24 h after operation.Conclusion:SFI can protect the small intestine mucosal barrier and other organs from second hit by reducing the polymorphonuclear leucocyte detaining and inhibiting TNF-α and IL-6.