Objective：This study aims to explore the effect of 11β-hydroxysteroid dehydrogenase（11β- HSD1） gene specific knockout on intestinal epithelial barrier function in mice. Methods：the 11β-HSD1 knockout model was established in C57BL/6J mice. The wild-type control group and 11β-HSD1 knockout group were fed with high-fat diet（from the 6th week，feed for 8 weeks）. The number of villi，crypts，goblet cells，and expression changes of ZO-1 and F4/80 were detected by immunohistochemistry. Results：11β-HSD1 gene knockout could change the villus length and goblet cell number of obese mice fed with high-fat diet，significantly reduce the intestinal epithelial inflammation and change the expression of tight junction protein in obese mice fed with high-fat diet. Conclusion：The changes of intestinal epithelial barrier function induced by high-fat diet are closely related to the effect of 11β-HSD1.