To investigate the effects and significance of chenodeoxycholic acid (CDCA) on pancreatic and intestinal injury in rats with severe acute pancreatitis (SAP). Methods Forty five male SD rats were randomly divided into three groups (15 rats of each group), namely SAP group, CDCA group and shamoperated (Sham) group. Rats in SAP group were first fed with universal diet for one week and then modeled by retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct. CDCA group were first fed with homogenous diet containing 0.5% CDCA for one week and then modeled, and tissue specimens were collected 24 hours after modeling. Tissue and serum specimens were collected. Firstly, the pathological changes of small intestine and pancreas tissues were observed by HE staining method; secondly, the levels of serum amylase, lipase, DAO, IFABP, D-Lac, IL-1β, IL-6, IL-18 and TNF-αwere detected by ELISA method. The apoptosis of intestinal mucosal epithelial cells was detected by TUNEL assay. Finally, the small intestine tissues were detected by WB method. The expression of TGR5 protein and inflammatory vesicles NLRP3 in small intestine tissue was detected by WB method. Results Compared with the SAP group, the histopathological damage of the pancreas and small intestine in the rats after CDCA intervention was reduced and the pathological score decreased (P＜0.05), and the levels of serum inflammatory factors (IL-1β, IL-6, IL-18, TNF-α) , amylase, lipase, and serum DAO, IFABP and D-Lac were also significantly reduced by ELISA (P＜0.05). TUNEL assay results showed that apoptosis of intestinal mucosal epithelial cells was also significantly alleviated compared with the SAP group (P＜0.05); finally, the expression of TGR5 protein as well as inflammatory vesicles NLRP3 in small intestinal tissues was also reduced after CDCA intervention. Conclusion CDCA significantly reduced pancreatic and intestinal injury in SAP rats and exerted certain protective effects, and this effect may be achieved by activating the TGR5 receptor in the intestine to inhibit the NLRP3 inflammasome.