Abstract: OBJECTIVE To observe the curative effect of Gancao Xiexin Decoction(GCXXT) on ulcerative colitis (UC) model rats and explore the regulation mechanism of related molecules in the pathways of IL-6/STAT3. METHODS 60 SD rats were randomly divided into 6 groups: control， TNBS/ethanol， mesalazine and GCXXT (2.93， 5.86， 11.72g/kg) groups. Blood serum was extracted to detect the content of ALT， AST， BUN and Cr. Colon tissues were observed by optical microscope. The expressions of protein of IL-6， STAT3 and phosphate STAT3 were evaluated by immunohistochemistry. The expressions of mRNA of IL-6 and STAT3 were analyzed by qPCR. RESULTS Compared with the blank group， AST in serum of model group increased obviously (P<0.01). However， ALT， BUN and Cr displayed no change (P>0.05). Pathological scores of colon tissues of model group increased significantly (P<0.01). The expressions of protein and mRNA of IL-6 and STAT3 in colon tissues increased in model group (P<0.01). Furthermore， the activation of STAT3 increased (P<0.01). Compared with the model group， AST in serum of rats of three groups treated with GCXXT decreased (P<0.01). Pathological scores of colon tissues of mesalazine group and medium dose GCXXT group decreased significantly (P<0.01). After the treatment of mesalazine or GCXXT， the expression of protein of IL-6， STAT3 and phosphate STAT3 reduced (P<0.01). The expression of mRNA of IL-6 and STAT3 decreased (P<0.01). CONCLUSION GCXXT can alleviate the pathological changes of colon， and medium dose of it can lead to satisfactory results. The mechanism may be related to its abilities to decrease expression of IL-6 in colonic tissue， inhibit IL-6/STAT3 signaling pathway and reduce the expression and activation of STAT3. These results showed that GCXXT is effective and safe in ameliorating ulcerative colitis.