Abstract: OBJECTIVE To observe the effects of berberine hydrochloride(BBR) on the colonic mucosal mechanical barrier in mice with ulcerative colitis(UC), and to explore the possible mechanisms of its therapeutic effects on UC. METHODS BALB/c mice were randomly divided into blank control group, model control group, low dose BBR group, middle dose BBR group, high dose BBR group and salazosulfapyridine positive control group. UC mouse model was established by dextran sulphate sodium(DSS), and then daily gavage administration was given for 7 days. During the course of experiment, the general conditions of mice were observed, and disease activity index(DAI) were assessed. At the end of treatment, colon tissue were sectioned and HE stained, and its pathological changes were observed under light microscope, the contents of LGR-5 and TERT were determined by Western blot, the expression level of claudin-1, occludin and ZO-1 were detected by immunohistochemical method. RESULTS Compared with model control group, the clinical and pathological symptoms of colitis in BBR groups were improved greatly, with their DAI were all decreased. After middle or high dose BBR treatment, the expression levels of LGR-5, TERT, claudin-1, occludin and ZO-1 of colonic tissue in UC mice were all increased when comparing with model control group, whose difference were statistically significant. CONCLUSION BBR can effectively relieve colitis in UC mice, the mechanism may be ralated to keeping the steady state of intestinal mucosal barrier by suppressing the destruction of intestines stem cells and tight junction proteins.