Abstract: Objective To observe the effects of Berberine (BBR) extracted from Chinese Goldthread Rhizome on colonic mucosal mechanical barrier in mice with ulcerative colitis (UC), and to explore the possible mechanisms of BBR's therapeutic effect. Methods BALB/c mice were randomly divided into five groups:model control group, low and high dose BBR group, positive control group and blank control group. UC model was established by dextran sulphate sodium, and daily gavage administration was given for 7 days. Disease activity index (DAI) of mice were assessed, colon tissue were sectioned and HE stained, and its pathological changes were observed, the contents of claudin-1, occludin and ZO-1 were detected by immunohistochemical method, the expression levels of LGR-5 and TERT were determined by Western Blot. Results Compared with those before the treatment, the DAI of UC mice after the treatment were all decreased (P<0.01), with their pathological symptoms of colitis improving to varying degrees; compared with model control group after the treatment, the DAI of high dose BBR group were decreased obviously (P<0.01), the expression levels of claudin-1, occludin and ZO-1 in high dose BBR group were all markedly increased (P<0.01), and the contents of LGR-5 and TERT in low and high dose BBR groups were all elevated (P<0.05). Conclusion Berberine can keep the steady state of intestinal mucosal barrier by suppressing the destruction of ISCs and tight junction proteins, thus effectively inhibit the colitis in UC mice. It is then proved to have a protective effect on the pathogenesis of UC.