This study aims to investigate the effect of five-flavor sophora flavescens enteric-coated capsules (FSEC) on TNF-α-induced inflammatory bowel disease and its molecular mechanism. Wistar Rats were divided divided into 6 groups: Normal control group (group A): normal diet, drinking water; Model group (group B): 100 μg/L TNF-α; FSEC high-dose group (group C): 100μg/L TNF-α + FSEC (432 mg/kg); FSEC medium-dose group (group D): 100 μg/L TNF-α + FSEC (216 mg/kg); FSEC low-dose group (group E): 100 μg/L TNF-α + FSEC (108 mg/kg); Positive control group (group F): 100 μg/L TNF-α + 500 mg/kg sulfasalazine (SAZ). Animals in each group were intragastrically administered twice daily for 7 days. Animals were sacrificed 24 hours after the last treatment and colon tissues were collected for subsequent experiments. The results of HE staining showed that the colonic tissue of TNF-α-fed animals appeared damage, while the colonic tissue of animals treated with FSEC was improved to various degrees, and the histological characteristics of colon were basically recovered in the high-dose group, suggesting that FSEC could be used to treat TNF-α-induced colonic tissue damage. According to the results of ELISA and immunohistochemistry, the recovery of colonic tissue structure in rats treated with different doses of FSEC might be related to the decrease of TNF-α, IL-6, IL-17, TLR-4 and NF-κB proteins expression. According to the results of Western blotting, TNF-α-pretreated IEC-6 cells cultured with medicated serum decreased the expression of TRIF and IFN-γ proteins. These results suggest that FSEC has a protective effect on ulcerative colitis (UC), and the mechanism may be through inhibiting the activation of TLR-4/NF-κB signaling pathway and preventing the release of related inflammatory factors.