To observe the effect of Wang's Baochi Pills on the expression of 5-hydroxytryptamine(5-HT) in the brain and intestinal tissues of rats with diarrhea-predominant irritable bowel syndrome(IBS-D) and its impact on the gut microbiota，explore some of the potential mechanisms of Wang's Baochi Pills in the treatment of IBS-D，and inherit and explore the application of classical formulas.Methods:The IBS-D model was established using a combination of senna leaf gavage and restraint stress.After successful modeling，the rats were randomly divided into the model group，Tongxiening group，Wang's Baochi Pills group，and a blank control group according to a random number table，with 10 rats in each group.The Wang's Baochi Pills and Tongxiening groups were administered the respective herbal suspensions，while the blank and model groups received an equal volume of distilled water by gavage，once daily for 14 days.The improvement of IBS-D-related symptoms and abdominal withdrawal reflex(AWR) scores in each group were assessed.The 5-HT expression in brain and intestinal tissues and changes in the gut microbiota were detected using immunohistochemistry and high-throughput sequencing，respectively.Results:Compared with the model group，the Wang's Baochi Pills group showed significant improvements in general condition，a decrease in Bristol stool scores，and a reduction in the number of stools after 2 hours(P<0.01).The expression of 5-HT in brain and intestinal tissues was significantly reduced(P<0.05)，and the diversity and abundance of the gut microbiota improved.Conclusion:Wang's Baochi Pills can alleviate the diarrhea symptoms and intestinal hypersensitivity in IBS-D model rats，reduce the expression of 5-HT in brain and intestinal tissues，and maintain the diversity of the gut microbiota.The mechanism may be related to the “microbiota-brain-gut” axis.