Abstract： Objective： To observe the clinical effect of Tongxie Anpi tang combined with Changweisan application for irritable bowel syndrome with diarrhea. Methods：A total of 118 cases of patients with irritable bowel syndrome with diarrhea were divided into two groups according to the random number table method，59 cases in each group. The control group was treated with Changweisan application，and the observation group was additionally treated with Tongxie Anpi tang based on the treatment of the control group. Before and after treatment， the levels of neuropeptide Y(NPY)， 5-hydroxytryptamine (5- HT) and Interferon- γ(IFN- γ) and the scores of Hamilton Depression Scale(HAMD)，Hamilton Anxiety Scale(HAMA) and Chinese medicine syndromes in the two groups were compared. Results： Before treatment， there was no significant difference being found in the comparison of NPY，5-HT and IFN-γ between the two groups(P＞0.05). After treatment，the levels of NPY，5- HT and IFN- γ in the two groups were improved when compared with those before treatment，and the levels in the observation group were lower than those in the control group，the difference being significant(P＜0.05). Before treatment，there was no significant difference being found in the comparison of HAMD and HAMA between the two groups (P＞0.05). After treatment，the scores of HAMD and HAMA in the two groups were improved when compared with those before treatment，and the scores in the observation group were lower than those in the control group，the difference being significant(P＜0.05). Before treatment， there was no significant difference being found in the comparison of Chinese medicine syndrome scores between the two groups(P＞0.05). After treatment，the Chinese medicine syndrome scores in the two groups were improved when compared with those before treatment，and the level in the observation group was lower than that in the control group， the difference being significant(P＜0.05). Conclusion： Tongxie Anpi tang combined with Changweisan application for irritable bowel syndrome with diarrhea has significant clinical effect， which can effectively improve abdominal discomfort and gastrointestinal function，relieve pain and inhibit bad mood.