To observe the effect and mechanism of Qingyi II Granules (QY) against the pancreas injury in rats with severe acute pancreatitis (SAP). Methods:Eighteen SD rats were randomly divided into fake operation group (group A)， SAP group (group B) and treatment group (group C). The rat SAP model was made by retrograde injection of 30 g/L sodium taurocholate into pancreatic duct. Group C was treated with 250 g/L Qingyi Ⅱ Granule (10 mL/kg)， once per 6 h， and group A and group B were treated with the same dose of saline in the same way. The expression of Hmgb1 mRNA in pancreatic tissue was detected by real-time PCR after 24 hours of modeling. The concentration of nitric oxide and endothelin-1 in pancreas was measured by enzyme-linked immunosorbent assay (ELISA). The pathological changes of pancreas were observed and the wet/dry weight ratio of pancreas was measured. Results:There were pancreas injury changes in group B， besides， expression of Hmgb1 mRNA was up-regulated and the levels of nitric oxide and endothelin-1 were increased; Qingyi Ⅱ Granule may cause that the expression of Hmgb1 mRNA in pancreatic tissue， the levels of nitric oxide and endothelin-1 concentration were decreased， thus reduced the degree of pathological damage of the pancreas. Conclusion:Hmgb1， nitric oxide and endothelin-1 may play an important role in SAP pancreatic injury. Qingyi II granules may reduce the expression of Hmgb1 mRNA in pancreatic tissue and decrease the concentration of nitric oxide and endothelin-1 to reduce the pathological changes of pancreatic tissue， thus protecting the pancreas injury.