Objective To investigate the effect of Shenmai injection on severe acute pancreatitis (SAP)-associated lung injury and the possible mechanism in rats. Methods The animals were randomly divided into three groups: sham operation group (sham group, n=10), severe acute pancreatitis (SAP group, n=10) and Shenmai injection treatment group (SM group,n=10). The rat model of SAP was induced by injection of 5% sodium taurocholate to the pancreatic duct. The rats in SM group were given Shenmai injection (8 mL/kg) via tail vein 10 min before sodium taurocholate injecting. 24 h after the model was made, 1 mL blood was drawn for serum amylase detection. Left lung tissues and pancreatic tissues were harvested for pathology and immunohistochemistry. Right lung tissue was homogenated for detection of myeloperoxidase (MPO) activity and levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Results There were no obvious damages to pancreas and lung in the sham group. While in the SAP group, the plasma amylase was greatly increased, the pancreatic lobular structures were severely damaged, and the pulmonary alveoli were destroyed with inflammatory cell infiltration. The MPO activity, MDA, TNF-α, and IL-1β levels in the SAP lung tissues were significantly increased compared with those in the sham group (P<0.01). ICAM-1 and caspase-3 were strongly positive in the lung tissues of SAP group. These parameters in the SM group were improved compared with those in the SAP group. Conclusion Shenmai injection has a protective effect on SAP-associated lung injury, and the mechanism may be related to the inhibition of apoptosis and reduction of oxygen free radical and inflammatory content.