Objective To investigate the effect of sanshensancao mixture on the histologic injury of colonic mucosa and the level of IL-12P70, TNF-α and IFN-γ in rats with ulcerative colitis(UC). Methods The rats were randomly divided into control group, model group and sanshensancao mixture group, with 10 rats in each group. The control group was fed with conventional diet, the sanshensancao mixture group and model group were established UC model by sodium trinitrobenzene sulfonate(TNBS)-ethanol induction method. Then 4.5 g /(kg.d) sanshensancao mixture was administered by gavage to the sanshensancao mixture group, and equal amount of normal saline was administered to the model group., After the treatment, all rats were evaluated for tissue damage injury (TDI) score of colon mucosa, and the levels of IL-12P70, TNF-α, and IFN-γ in the colon mucosa were measured by ELISA. Results Compared with the model group, the TDI score of the sanshensancao mixture group decreased significantly, and the level of IL-12P70, TNF-α and IFN-γ decreased significantly. Conclusion Sanshensancao mixture relieves the histological damage of colonic mucosa in rats with UC and reduces the level of IL-12P70, TNF-α and IFN-γ.