Abstract： Objective： To observe the clinical effect of Modified Dachengqi Decoction combined with continuous renal replacement therapy (CRRT) and urinastatin on severe acute pancreatitis (SAP) and its effect on intestinal mucosal barrier function and serum soluble cluster of differentiation 14 subtype (sCD14- st) levels. Methods：A total of 140 cases of SAP patients were randomly divided into the control group and the observation group，with 70 cases in each group. During treatment，there were 2 cases of drop-out in the control group and 3 cases in the observation group. The control group was treated with CRRT and urinastatin， and the observation group was additionally treated with Modified Dachengqi Decoction based on the treatment of the control group. Both groups were treated for 2 weeks. Clinical effects， as well as traditional Chinese medicine (TCM) syndrome scores， scores of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ)， intestinal mucosal barrier function indicators [D-lactate， diamine oxidase (DAO)， and amylase (AMS)]， and the levels of serum factors [sCD14-st and monocyte chemotactic protein-1 (MCP-1)] were compared before and after treatment between the two groups. Results： After treatment，the total effective rate was 94.03% in the observation group and 82.35% in the control group， the difference being significant (P＜0.05). After treatment，TCM syndrome scores and APACHE-Ⅱscores in the two groups were decreased when compared with those before treatment (P＜0.05)，and the scores in the observation group were lower than those in the control group (P＜0.05). After treatment，the levels of D-lactate， DAO， and AMS in the two groups were decreased when compared with those before treatment (P＜0.05)， and the three levels in the observation group were lower than those in the control group (P＜0.05). After treatment， the levels of sCD14-st and MCP-1 in serum in the two groups were decreased when compared with those before treatment (P＜0.05)， and the above two levels in the observation group were lower than those in the control group (P＜0.05). Conclusion： Modified Dachengqi Decoction combined with CRRT and urinastatin has significant curative effects in treating SAP，which can obviously down-regulate levels of sCD14-st and MCP-1，improve intestinal mucosal barrier function and TCM syndromes，and effectively control the progression of the disease.