Abstract: OBJECTIVE To explore the clinical efficacy and the brain-gut peptide effect of Tongxie Yao Fang combined with Sijunzi Decoction in the treatment of Irritable Bowel Syndrome (IBS-D) patients with diarrhea type. METHODS 53 patients diagnosed with IBS-D according to Rome Ⅲ standards were randomly divided into two groups. 27 patients in treatment group were treated with Tongxie Yao Fang combined with Sijunzi Decoction， and 26 patients in control group were given by the Pinaverium Bromide and Bifidobacterium Tablets for four weeks. The changes of clinical symptom index， quality of life (IBS-QOL)， neuropeptide Y (NPY)， calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) before and after treatment were observed. RESULTS The total effective rates in treatment group were 92.6%， significantly higher than 76.9% in control group ( P <0.05). The clinical symptom index in treatment group was significantly lower than that of the control group after treatment( P <0.05). And the score of IBS-QOL in treatment group was higher than that in control group ( P <0.05). The level of plasma NPY in both groups increased significantly after treatment， while CGRP and VIP levels decreased significantly ( P <0.05， P <0.01)， and the difference between the two groups was statistical significance ( P <0.05). CONCLUSION Tongxie Yao Fang combined with Sijunzi Decoction can significantly improve clinical symptom and QOL of IVS-D patients， and its mechanism may through the increase of plasma NPY level and the decrease of CGRP and VIP level， regulating the balance of brain-gut peptide secretion.