Abstract： Objective： To observe the clinical efficacy of Tiaozang Shuli Prescription administered via rectal instillation combined with Vedolizumab in treating active-phase ulcerative colitis of spleen deficiency and dampness obstruction type，and its effects on intestinal microbiota，anti-inflammatory factors，serum type ⅩⅥ collagen （col- 16）， and GATA binding protein-3 （GATA-3）. Methods： A total of 90 patients with ulcerative colitis of spleen deficiency and dampness obstruction type treated at Zhoukou Hospital of Traditional Chinese Medicine from April 2022 to April 2024 were selected and divided into a control group and an observation group， with 45 cases in each group， using a random number table method. The control group was given intravenous Vedolizumab for oral administration，while the observation group received Tiaozang Shuli Prescription via rectal instillation on the basis of the control group. Both groups were treated for eight weeks. Clinical efficacy was compared between the two groups after treatment. Scores for abdominal pain， purulent and bloody stool， poor appetite， fatigue and reluctance to speak， abdominal bloating， and limb weariness， as well as the modified Mayo activity index scores and the Inflammatory Bowel Disease-Quality of Life Questionnaire （IBDQ） scores were evaluated before and after treatment. Levels of serum diamine oxidase（ DAO），GATA-3，tumor necrosis factor-α（ TNF-α），col-16，interleukin-10（ IL-10），and Dlactic acid （D-LA） as well as the number of Staphylococcus，Enterococcus，and Lactobacillus in stool were compared between the two groups. Adverse reactions during treatment were recorded，and the incidence of adverse reactions was calculated. Results：After treatment，the clinical efficacy in the observation group was superior to that in the control group （P＜0.05）. Scores for abdominal pain， purulent and bloody stool， poor appetite， fatigue and reluctance to speak， abdominal bloating， limb weariness， and the total score of traditional Chinese medicine syndrome in both groups were decreased compared to those before treatment （P＜0.05）， with the observation group achieving lower scores than the control group （P＜0.05）. Mayo scores and levels of TNF-α，GATA-3，DAO，col-16，and D-LA in both groups were decreased compared to those before treatment （P＜0.05），with the observation group achieving lower indicators than the control group （P＜0.05）；IBDQ scores and IL-10 levels in both groups were increased compared to those before treatment（ P＜0.05），with the observation group achieving higher levels than the control group（ P＜0.05）. The number of Staphylococcus and Enterococcus in both groups was decreased compared to that before treatment （P＜ 0.05）， with the observation group achieving less numbers than the control group （P＜0.05）； the number of Lactobacillus was increased in both groups compared to that before treatment （P＜0.05）， with the observation group achieving a more number than the control group （P＜0.05）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. Conclusion：Tiaozang Shuli Prescription administered via rectal instillation combined with Vedolizumab for the treatment of active-phase ulcerative colitis of spleen deficiency and dampness obstruction type can regulate intestinal microbiota， suppress inflammation， reduce intestinal mucosal damage，alleviate symptoms，and improve patients' quality of life and clinical efficacy，with high safety.