Objective:To investigate the effect of combined reagent of different particles of Compound Lizards Powder on the protein expression of myeloid differentiation factor88(MyD88) and tumor necrosis factor receptor-associated factor-6(TRAF6) that in TLRs/MyD88 signaling pathway and the content of downstream inflammatory factors tumor necrosis factor-α(TNF-α)in rat model of ulcerative colitis(UC),and discuss its mechanisms on UC. Methods84 male SD rats were randomly divided into six groups as the normal control group, model group, sulfasalazine tablets (SASP) treatment group, treatment groups of Compound Lizards Powder filtrated through 80 mesh ,100 mesh ,80+100 mesh equivalent mix respectively,14 rats in each group. The control group was received the enema treatment with 0.9%NaCl solution, and the other groups were received the enema treatment with three nitrobenzene sulfonic acid (TNBS) to establish the UC model. After successful modeling, the control and model group were administered intragastrically with 0.9%NaCl solution and the other groups were administered intragastrically with the corresponding drugs,with a course of 14 days. After treatment for 14 days,all rats were anesthetized and the blood were collected from abdominal aorta and preserved at low temperature after centrifugation. The lesion of colon tissue were obtained and embedded. The pathological changes of colonic mucosa were observed by HE staining. The situ protein expressions of MyD88 and TRAF6 in colon tissues were determined by immunohistochemistry. The level of serum TNF-α was detected by enzyme linked immunosorbent assay(ELISA).  Results:Compared with the normal control group,the protein expression of MyD88 and TRAF6 and the level of TNF-α in the other groups were increased,with statistically significant differences(P<0.05). Compared with the model group,the levels of all indicators in each treatment group were decreased,with statistically significant differences(P<0.05). Comparison of SASP treatment group and treatment groups of Compound Lizards Powder,the treatment effects of the Compound Lizards Powder filtrated through 80+100 mesh equivalent mix were best,with statistically significant differences(P<0.05). There were no statistically significant differences on the effects between the SASP treatment group and treatment group of Compound Lizards Powder filtrated through 80 mesh or 100 mesh(P>0.05). Comparison of treatment groups of Compound Lizards Powder,the levels of all indicators were obviously decreased in the treatment group of Compound Lizards Powder filtrated through 80+100 mesh equivalent mix,with statistically significant differences(P<0.05).  Conclusion:The combined reagent of different particles of Compound Lizards Powder could inhibit the protein expression of MyD88 and TRAF6 that in TLRs/MyD88 signaling pathway and decrease the level of downstream inflammatory TNF-α,which suggested that its main mechanism in the treatment of ulcerative colitis were blocking the inflammatory reaction,regulating immunity,restoring intestinal barrier,maintaining intestinal homeostasis and promoting intestinal mucosal repair.