Abstract：Objective：To explore the curative effect mechanism of modified Sishen Pills for ulcerative colitis. Methods：A total of 30 female C57BL/6 mice were selected as experimental subjects and randomly divided into the normal group， the model group， the positive control group， the high- dose group of modified Sishen pills (the hight-dose group) and the low-dose group of modified Sishen Pills (the low-dose group)，with 6 cases in each group. After 1 week of adaptive feeding，a model of ulcerative colitis induced by sodium dextran sulfate was constructed and given by intragastric administration. The mental state of the mice was observed and the mice were weighed every day during the experiment. After the experiment， the Disease Activity Index (DAI)， pathological indexes of colon tissue， and the expression levels of interleukin-6 (IL-6)， interleukin-10 (IL-10)， Toll-like receptor 4 (TLR4)， p65 and phosphorylated P65 (p-p65)，and β-actin protein were compared among the five groups. Results：Compared with those in the normal group，DAI score，fecal viscosity score，blood stool score，IL-6 level，and expression levels of TLR4， p65 and p- p65 in colonic tissue in the model group were significantly increased (P＜0.05)， and colon length and IL- 10 level were significantly decreased (P＜0.05). Compared with those in the model group，DAI score in the positive control group and the high-dose group were significantly decreased (P＜ 0.05)，and there was no significant change in DAI score in low-dose group (P＞0.05)；colon length in the high- dose group was significantly increased (P＜0.05)，and colon length in the positive control group and the low-dose group were not significantly increased (P＞0.05)；fecal viscosity scores in the positive control group，the high-dose group and the low-dose group were significantly decreased (P＜0.05)；there was no significant change in blood stool scores in the positive control group，the high- dose group and the lowdose group (P＞0.05)；IL-6 level in the high-dose group was significantly decreased (P＜0.05)，and the IL-6 level in the positive control group and the low-dose group did not decrease significantly (P＞0.05)； IL-10 levels in the high- and low-dose groups were significantly increased (P＜0.05)， and the level of IL-10 in the positive control group was not significantly increased (P＞0.05)；the relative expression levels of TLR4，p65 and p-p65 in colonic tissue in the positive control group，the high-dose group and the lowdose group were significantly decreased (P＜0.05). In terms of pathological changes，goblet cells in colonic tissue in the model group were significantly reduced， crypt structure was seriously damaged， and there was obvious inflammatory infiltration. Compared with those in the model group， the above pathological changes of colonic tissue in the positive control group and the high- dose group were significantly improved，and the above pathological changes in the low-dose group were slightly improved. Conclusion： Modified Sishen Pills for mice with ulcerative colitis can improve their clinical symptoms and pathological indexes of colon tissue to a certain extent， and its mechanism may be related to TLR4/NF- κB signaling pathway.