Abstract: Objective To explore the effect of acupuncture combined with Traditional Chinese Medicine therapy on diarrehea-predominant pattern irritable bowel syndrome (IBS-D) patients. Methods A total of 80 patients with IBS-D who were treated in our hospital from March 2015 to April 2017 were selected, and they were randomly divided into observation group (n=40) and control group (n=40) according to the random number table method. The control group was treated with Traditional Chinese Medicine, and the observation group was treated with acupuncture therapy based on the control group. The clinical effect, emotional related indicators and neuroactive substances level were compared between the two groups. Results The total effective rate of patients in observation group was 92.5%, and the total effective rate of patients in control group 72.5%, the total effective rate in observation group was significantly higher than that of control group (P<0.05). Before treatment, there were no significant differences in the scores of elf-rating depression scale (SDS) and self-rating anxiety scale (SAS) between the two groups (all P>0.05); after treatment, the scores of SDS and SAS in the two groups were significantly lower than those before treatment (all P<0.05), and the scores of SDS and SAS in observation group was significantly lower than those of control group (all P<0.05). Before treatment, there were no significant differences in the levels of neuropeptide Y (NPY), 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP) between the two groups (all P>0.05); after treatment, the levels of NPY, 5-HT and CGRP in the two groups were significantly lower than those before treatment (all P<0.05), and the levels of NPY, 5-HT and CGRP in observation group was significantly lower than those of control group (all P<0.05). Conclusion The acupuncture combined with Traditional Chinese Medicine therapy has remarkable effect in treatment of IBS-D, which can obviously improve the emotional and nerve function of patients.