The study aimed to explore the prevention and treatment effect of Coptis chinensis extract (CCE) on ulcerative colitis (UC) induced by sodium dextranate sulfate (DSS) in mice. Six groups of sixty C57BL/6 mice were randomly selected, namely control group (CON), DSS model group, mesalazine (MES) positive control group (200 mg/kg), low CEE (CEE-L, 600 mg/kg), medium CEE (CEE-M, 1 000 mg/kg), high CEE (CEE-H, 1 400 mg/kg) dose group. The pre-test period was seven days and the formal test preiod was 14 days. The results showed that compared with DSS group, CCE group extremely inhibited weight loss (P<0.01), DAI score and colon length of UC mice were extremely increased (P<0.01). CEE group improved the pathological injury of colon tissue in UC mice, the intestinal villi and crypt structure were restored, and there was a decrease in the invasion of inflammatory cells. Compared with DSS group, the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA in colon of CEE group were extremely down-regulated (P<0.01). At the phylum level, there was a substantial decrease in the relative abundance of Proteobacteria and Campylobacter in the CEE group when compared to the DSS group. There was a notable rise in the relative abundance of Verrucomicrobacteria in the CEE-L and CEE-M groups, and the relative abundance of Bacteroidetes and Desulphurobacteria in CEE-M and H groups were significantly increased. In terms of genus level, in the CEE-M and CEE-H groups, there was a notable decrease in the relative abundance of Escherichia-Shigella, but an apparent rise in the relative abundance of Ackermania in the CEE-L and CEE-M groups. The study indicates that CCE can play a preventive and protective role in UC mice by inhibiting the expression of inflammatory factors and maintaining the homeostasis of intestinal flora.