Objective To investigate the mechanism of radix salviae miltiorrhizae (RSM) injection in treatment of pancreatitis through observing the changes of activity of nuclear factor-kappa B (NF-κB) in pancreas of rats with severe acute pancreatitis (SAP) and the influence of RSM injection upon NF-κB in pancreas tissue. Methods Seventy-five rats were randomly divided into 3 groups: normal control group, SAP group and RSM treatment group, which were injected with normal saline, normal saline or RSM in the peritoneal cavity, respectively. The model of SAP rats was made by injecting L-arginine into peritoneal cavity and by subcutaneous injection at the same time. The concentrations of amylase in plasma and in ascites were measured respectively, and the expression of NF-κB in pancreas tissues was determined by immunohistochemistry. Results The levels of amylase in plasm and ascites in SAP group and RSM treatment group increased significantly with the increased expression of NF-κB in pancreas tissue, but it was also found that both the level of amylase and the expression of NF-κB in RSM treatment group were significantly lower compared with those in SAP group, and the survival time of RSM treatment group was longer than SAP group with less pathological injury in the pancreas tissues. Conclusion RSM may be effective for the treatment of pancreatitis by degrading the expression of NF-κB.