Abstract: OBJECTIVE  To explore the treatment and mechanism of Qingchang Huashi Decoction on ulcerative colitis mice.METHODS   The mouse model of ulcerative colitis was induced by DSS, and the mice were treated with drug intervention treatment and weighed during the experiment. At the end of the experiment, the length of the colon was measured, and pathological sections of the colon were made. The contents of IL-6 and TNF-α in colon tissue were detected by enzyme-linked immunoassay. Gas chromatography-mass spectrometry was used to determine the concentrations of butyric acid and isobutyric acid in the contents of the colon. High throughput sequencing technology based on 16S rRNA amplification was used to detect and analyze the composition and abundance of mouse fecal flora.RESULTS   Compared with the healthy control group, mice with ulcerative colitis showed weight loss, enlarged spleen, shortened colon length (P < 0.05, P < 0.01), increased levels of IL-6 and TNF-α in colon tissue (P < 0.01), decreased butyric acid and isobutyric acid in colon contents (P < 0.01), and changed gut flora composition and abundance.After treatment with Qingchang Huashi Decoction, the weight of the mice was increased significantly, the spleen enlargement was reduced, and the length of the colon was increased. Compared with the model group, the colon pathological damage was ameliorated and the levels of IL-6 and TNF-α in colon tissue were reduced. After treatment, the contents of butyric acid and isobutyric acid in the colon contents increased significantly, and the unbalanced gut flora was adjusted to approaching the normal state.CONCLUSION   The mechanism of Qingchang Huashi Decoction in treating ulcerative colitis is related to its regulating the gut flora, increasing the contents of butyric acid and isobutyric acid in the colon, and reducing the levels of pro-inflammatory factors including IL-6 and TNF-α.