Abstract: OBJECTIVE  To explore the treatment and mechanism of Baitouweng decoction on ulcerative colitis mice.METHODS  Colitis mice were induced by DSS and treated with or without Baitouweng decoction. During experiment, body weight of mice, the symptom of diarrhea and bloody stool were recorded. At the end of experiment, the length of colon was measured, colonic pathology was observed after HE staining, the expression of cytokines was evaluated by qPCR, the construction of gut microbiota was detected by 16S rRNA, the concentration of short chain fatty acids was measured by gas chromatography-mass spectrometry.RESULTS  Compared with the healthy mice, the body weight and the length of colon decreased in colitis mice(P < 0.01), the construction of colon was disorder with infiltration of inflammation cells, and the expressions of IL-1β, IL-6 and TNF-α was upregulated(P < 0.05, P < 0.01). But the expression of anti-inflammatory cytokines were not different between these two groups. Moreover, dysbacteriosis and low level of short chain fatty acids were observed. After Baitouweng decoction treatment, the weight of mice and the length of colon were increased(P < 0.05, P < 0.01). The expressions of pro-inflammatory cytokine, such as IL-1β, IL-6 and TNF-α, was downregulated(P < 0.05, P < 0.01). And the construction of gut microbiota was rebalanced especially in DSS+BTW-H group. The contents of butyric acid and valeric acid increased significantly(P < 0.05, P < 0.01).CONCLUSION  Baitouweng decoction has therapeutic effect on DSS-induced colitis through rebalancing gut microbiota and short chain fatty acids.