Abstract：Objective：To observe the clinical effect of the therapy of modified huoxiang zhengqi powder combined with western medicine on the treatment of irritable bowel syndrome with diarrhea(IBS-D)，and its effect on the levels of calcitonin gene-related peptide(CGRP) and vasoactive intestinal peptide(VIP). Methods：A total of 75 patients with IBS-D were selected and divided into the control group and the observation group by random number table method，with 37 and 38 cases in each group respectively. The control group was treated with trimebutine maleate tablets and bifidobacterium quadruple viable tablets，and the observation group was additionally treated with modified huoxiang zhengqi powder based on the treatment of the control group. Both groups were treated for four weeks. The clinical effect in the two groups was compared. The score of symptoms， score of Irritable Bowel Syndrome-Quality of Life Scale(IBS-QOL) ， and the levels of CGRP and VIP were compared between the two groups before and after treatment. Results： The total effective rate was 92.11% in the observation group，higher than that of 72.97% in the control group(P＜0.05). After treatment，the scores of abdominal pain， abdominal distension，defecation frequency and stool trait in both groups were decreased when compared with those before treatment，and the scores of the above four symptoms in the observation group were lower than those in the control group， differences being significant(P＜0.05). After treatment， the scores of emotional status， behavioral disorder， body consciousness，dietary influence，health concern，social function，sexual behavior，daily social and the total score of IBSQOL in both groups were increased when compared with those before treatment(P＜0.05)，the above scores and the total score in the observation group were higher than those in the control group(P＜0.05). Each score in IBS- QOL and the total score in the observation group were higher than those in the control group(P＜0.05). After treatment，the levels of CGRP and VIP in both groups were decreased when compared with those before treatment， and the levels of CGRP and VIP in the observation group were decreased more significantly than those in the control group，differences being significant(P＜0.05). Conclusion：Modified huoxiang zhengqi powder combined with western medicine can improve the clinical symptoms of IBSD patients，improve their quality of life，and reduce the levels of CGRP and VIP.