Abstract：Objective：To observe the clinical effect of Tongxie Sishen tang combined with western medicine for diarrheapredominant irritable bowel syndrome(IBS- D) with the liver depression and spleen deficiency syndrome，and its effect on levels of calcitonin gene related peptide(CGRP) and vasoactive intestinal peptide(VIP). Methods： A total of 136 cases of patients were randomly divided into the control group and the observation group，68 cases in each group. Both groups were given trimebutine maleate dispersible tablets and compound eosinophil- lactobacillus enteric- coated capsules； the observation group was additionally given oral administration of Tongxie Sishen tang based on syndrome differentiation. Both groups were continuously treated for six weeks. Before and after treatment，the scores of the liver depression and spleen deficiency syndrome，the degree of abdominal pain，and IBS Syndrome Severity Scale(IBS-SSS) were evaluated；the levels of CGRP and VIP were detected. The clinical effect was compared between the two groups. Results：After treatment，the clinical effect in the observation group was better than that in the control group(P＜0.05). The scores of the liver depression and spleen deficiency syndrome， the degree of abdominal pain， and IBS- SSS in the two groups were decreased when compared with those before treatment(P＜0.01)，and the three scores above in the observation group were lower than those in the control group(P＜0.01). The levels of CGRP and VIP in serum in the two groups were decreased when compared with those before treatment(P＜0.01)，and the two levels above in the observation group were lower than those in the control group(P＜0.01). Conclusion：For IBS- D patients with the liver depression and spleen deficiency syndrome，the additional oral administration of Tongxie Sishen tang on a basis of trimebutine maleate and compound eosinophil- lactobacillus can further relieve clinical symptoms of IBS-D，inhibit the expression of CGRP and VIP，regulate the levels of gastrointestinal hormones，and improve clinical effect.