OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis （SAP）mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ，interleukin 10（IL-10），IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin，ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ，abdominal distension symptoms of SAP model rats were significantly relieved ，and their mental state recovered better ；the levels of serum amylase and IL- 18 in serum were decreased significantly （P＜0.05），while the level of IL- 10 was increased significantly （P＜0.05）. The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced ， the degree of intestinal epithelial cell structural disorder was alleviated ，and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly （P＜0.05），and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ，reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.