Background Traditional Chinese medicine has been used widely for many years in China to treat acute pancreatitis.We have investigated the effects of Dachengqi decoction on intestinal mucosal permeability and outcome in patients with severe acute pancreatitis (SAP).Methods Forty patients with sustained SAP that required admission to the surgical intensive care unit were enrolled prospectively in the study. All of these patients were divided randomly into the Dachengqi decoction group (n=20) and control group (n=20) on admission. Intestinal permeability was assessed by measuring absorption of two metabolically inert markers, lactulose (L) and mannitol (M), which were administered orally. Serum concentrations of endotoxin (lipopolysaccharide, LPS) and the ratio of lactulose to mannitol in urine (L/M) were detected in all patients.Results Compared with those in the control group, urinary L/M ratio decreased significantly in the Dachengqi decoction group on the 7th day after admission (P=0.001). Also, serum concentrations of LPS were reduced on the 5th and 7th day after admission (P=0.006, P=0.008, respectively). Incidence of multiple organ dysfunction syndrome (MODS) and pancreatic infection was significantly lower in the Dachengqi decoction group compared with those in the control group (P=0.038, P=0.025, respectively).Conclusion Dachengqi decoction may promote the recovery of intestinal mucosal permeability and decrease the incidence of MODS and pancreatic infection in patients with SAP.