Objective To study the effects of large dose anisodamine (654-2) combined with ulinastain on severe acute pancreatitis (SAP).Methods 100 healthy adult SD rats which were fasted 12 hours before experiment and were allowed drinking water freely,were divided to 5 groups randomly (random number):normal control group,SAPgroup,SAP + Ulinastain group,SAP + Anisodamine group,SAP +Ulinastain + Anisodamine,there were 20 rats in every group.To observe the levels of diastase,phospholipase A2 (PLA2) and endotoxin and pathology of rats in every group.Another cohort of 60 SD rats were divided into 3 groups:SAP group,SAP + Ulinastain group,SAP + Ulinastain + large dose Anisodamine group,survival periods were observed.Results The levels of diastase,PLA2 and endotoxin in SAP rats were higher than those in 3 SAP with treatment groups (P ＜ 0.05).The histopathological changes were most severe in SAP group.All of 3 markers in 3 SAP with treatment groups decreased obviously,and anisodamine alone was effective to treat SAP,but the effect of UTI + 654-2 was better than UTI or 654-2 alone,and histopathological changes were mild in this group treated with UTI + 654-2.Conclusions Anisodamine could effectively relax the Oddi sphincter thereby decreasing the hydrostatic pressure inside the bile duct and pancreatic duct.Ulinastain is a kind of proteinase inhibitor suppressing many kinds of enzymes and in tern to stabilize lysosomal membrane and inhibit the release of lysosomal enzyme.Combination of the large dose Anisodamine with Ulinastain could inhibit the overexpression of inflammationarv factors in SAP,thereby lessening the severity of viscera injury.