Objective　To investigate the effect of Xiaoer Fuxie Waifu powder on intestinal Cajal cells (ICC) and the expression of vasoactive peptide receptor 1 (VIP-R1) in rats with diarrhea. Methods　Thirty Wistar rats were divided randomly into three groups: control group, model group, and treatment group (10 each). Folium sennae (2ml/100g) was gavaged to reproduce the diarrheal model. Xiaoer Fuxie Waifu powder was applied topically in the treatment group. Transmission electron microscope was used to observe the changes in ultrastructure of ICC after application of the drug. Immunohistochemistry was used to observe the distribution of VIP-R1 in the intestine of diarrheic rats. RT-PCR and Western blotting were used to determine the expressions of mRNA and protein of VIP-R1. Results　The ultrastructure of ICC showed that the drug treatment could normalize the cellular morphology and gap junction. VIP-R1 was found to be distributed mainly between circular muscle and longitudinal muscle, in the myenteric nerve plexus of the small intestine, and was found around the epithelial cells in the mucosal layer of the colon and lamina propria cells. Xiaoer Fuxie Waifu powder inhibited the secretion of VIP-R1 and down-regulated the mRNA and protein expression of VIP-R1. Conclusion　Xiaoer Fuxie Waifu powder can repair the injured ICC of diarrheic rats and cure diarrhea by down-regulating the expression of VIP-R1. DOI: 10.11855/j.issn.0577-7402.2015.01.05