OBJECTIVE: To observe the effect of Banxia Xiexin decoction on nuclear transcription factor κB p65 (NF-κB p65), NF-κB inhibitory protein α (IκB-α) and Toll-like receptor 4 (TLR4) in colon tissue of rats with ulcerative colitis (UC), and explore the possible mechanism for UC treatment. METHODS: Rats were randomly divided into normal group (normal saline), model group (normal saline), Sulfasalazine enteric coated tablet (SASP, positive group, 0.3 g/kg), Banxia Xiexin decoction low-dose, medium-dose, high-dose groups (3.9, 7.8, 11.7 g/kg), 8 in each group. Except for normal group, other groups were used trinitrobenzene sulfonic acid-ethanol method to reduce UC model. After modeling, they were administrated, ig, once a day, for 3 weeks. After administration, NF-κB p65, IκB-α, TLR4 mRNA and protein expressions in colon tissue of rats in each group were detected. RESULTS: Compared with normal group, NF-κB p65, IκB-α, TLR4 mRNA and protein expressions in colon tissue of rats in other groups were significantly increased (P<0.05). Compared with model group, NF-κB p65, IκB-α, TLR4 mRNA and protein expressions in colon tissue of rats in each administration group were significantly decreased (P<0.05); showing certain dose-dependent, and the decreasing degree of above indexes in colon tissue of rats in Banxia Xiexin decoction high-dose group were higher than SASP group (P<0.05). CONCLUSIONS: Banxia Xiexin decoction can down-regulate the NF-κB p65, IκB-α, TLR4 mRNA and protein expressions in colon tissue of UC rats, which may be one of the mechanisms for UC treatment.