OBJECTIVE: To explore the underlying mechanism of action of Tongxieyaofang decoction in rats with visceral hypersensitivity using proteomics technology.METHODS: Twenty-four female Sprague-Dawley rats were randomly divided into three groups: control group, irritable bowel syndrome(IBS) group and Tongxieyaofang treatment group. An IBS model, characterized as visceral hypersensitivity, was established using the odour of mothballs as conditional stimulation and colorectal distension combined with classic physical restraint as non-conditional stimulation. Rats were intragastrically treated with Tongxieyaofang(2 or 4 m L · kg~(-1)· d~(-1))for 4 weeks. On the 45 th day, the rats were dissected and the colonic mucosal proteins were extracted. Differential protein spots were screened by fluorescent two-dimensional differential gel electrophoresis(2 D-DIGE), and identified by matrix-assisted laser desorption/ionisation time of flight mass spectrometry(MALDI-TOF-MS). Western blotting experiments were performed to verify the changes observed in 2 D-DIGE and MALDI-TOF-MS.RESULTS: It was found that the visceral sensitivity of rats in the Tongxieyaofang treatment group(4 m L/kg) was lower than that in the IBS group(P