OBJECTIVE: To observe the effects of the Bupi Hewei(BPHW) decoction on diarrhea and intestinal flora disorder induced by 5-fluorouracil(5-FU) and investigate the possible mechanism underlying these actions.METHODS: Thirty-five male Sprague-Dawley rats were randomly divided into four groups: normal control, 5-FU, 5-FU + BPHW decoction(10.5 g/kg for 5 consecutive days), and 5-FU + Bacillus licheni-formis capsule groups(0.2 g/kg for 5 consecutive days). Animal models were established via the intraperitoneal injection of 5-FU(30 mg/kg for 5 consecutive days). At the end of the treatment period, diarrhea was assessed, and the change of the intestinal flora was examined using 16 S r DNA highthroughput sequencing. Interleukin(IL)-17, IL-21,IL-6, IL-10, RAR-related orphan receptor gamma(RORγt), and forkhead box P3(Foxp3) expression in the jejunum was detected using immunohistochemistry, quantitative real-time polymerase chain reaction(PCR), Western blotting, and enzymelinked immuno sorbent assay.RESULTS: In this study, the BPHW decoction effectively lowered the diarrhea score, increased the proportions of Bacteroidetes and Prevotellaceae-Alloprevotella species, and reduced the proportions of Proteobacteria, Escherichia-Shigella, Ruminococcaceae NK4 A214, and Ruminococcaceae UCG-005 species in the rat intestine after 5-FU chemotherapy. In addition, the BPHW decoction significantly suppressed the expression of IL-17, IL-21, IL-6, IL-10,RORγt, and Foxp3 in the jejunum.CONCLUSION: Our findings suggest that the BPHW decoction can improve the intestinal immune balance and reduce intestinal inflammation by targeting T helper cell/T regulatory cell-associated factors.