Objective To explore the beneficial effects of continuous hemodiafiltration (CHDF) combined with enalapril on renal and intestinal function in rats with severe acute pancreatitis ( SAP). Methods Sixty Sprague-Dawley rats were randomly divided into a control group and four treatment groups: SAP model, CHDF, enalapril, and CHDF + enalapril. Rats in the treatment groups were induced with SAP using sodium taurocholate. After modeling, the CHDF group was given CHDF for 12 h, and the enalapril group was given enalapril 10 mg / kg / d by gavage, for 1 day. The CHDF + enalapril group was given both treatments simultaneously. Histopathological changes in the pancreas, kidney and intestinal mucosa were observed by hematoxylin and eosin staining. The plasma levels of endotoxin (ET) and D-lactic acid (D-LC), and serum levels of amylase (AMY), blood urea nitrogen ( BUN) and creatinine ( Cr) were measured. A fluorescein isothiocyanate-dextran permeability test was used to examine intestinal permeability. Western blotting was used to detect expression of α-vascular smooth muscle actin (α-SMA), E-cadherin, high mobility groupbox protein 1 ( HMGB1) and occludin. Results Compared with the model, CHDF + enalapril had the following effects in rats with SAP: effectively alleviated damage to the pancreas, kidney and intestinal mucosal tissues; significantly reduced intestinal mucosal permeability, the levels of serum AMY, BUN and Cr and plasma ET and D-LC, and expression of α-SMA and HMGB1 in tissues; and significantly increased expression of E-cadherin and occludin. The combined action effect was better than that of either single treatment. Conclusions CHDF combined with enalapril significantly improved renal and intestinal tissue damage caused by SAP, which contributed to the recovery of renal and intestinal function.