Objective:To investigate the efficacy and interventional mechanism of Tongxieyao Formula (TXYF) on rat model with irritable bowel syndrome (IBS) due to liver depression and spleen deifciency. Methods:75 newborn SD rats were randomly divided into groups A, B, C, D and E. Except group A, the rats in other groups were treated with senna and strained stress to establish IBS models due to liver depression and spleen deifciency. Groups A and B were fed with intra-gastric normal saline, group C pinaverium bromide, groups D and E TXYF. After treatment, animals were sacriifced to excise colons, and modiifed toluidine blue staining was applied to observe the changes of colonic mucosal mast cell (MC) count and de-granulation conditions in rats. Then the levels of 5-hydroxytryptamine (5-HT), P substance (SP), calcitonin gene-related peptide (CGRP) in blood samples were detected. Results:The counts of colonic mucosal MC and de-granulation increased signiifcantly in model control group. The levels of 5-HT, SP signiifcantly decreased while CGRP increased in C, D and group Es. Conclusion:TXYF can play its role of improving gastrointestinal mobility and reduce visceral sensitivity so as to treat IBS through reducing the counts of colonic mucosal MC and de-granulation as well as the levels of serum 5-HT and plasma SP, and increasing the level of CGRP in IBS model rats.