OBJECTIVE: To investigate the mechanism by which Daifan San(DFS) prevents and treats primary biliary cirrhosis(PBC) via the forkhead box P3(Fox P3) and interleukin(IL)-23/IL-17 A signaling pathways.METHODS: Ninety C57 BL/6 mice were randomly divided into the control, model, DFS low-dose, DFS middle-dose, DFS high-dose and ursodeoxycholic acid(UDCA) groups(n = 15 per group). A mouse model of PBC was induced using polyinosinic polycytidylic acids(poly I:C). Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry. The inflammatory cytokines and antimitochondrial autoantibody(AMA) levels were detected via enzyme-linked immunosorbent assays. The expressions and location of type Ⅰ collagen, typeⅢ collagen, cytokeratin 19 and Fox P3 in the liver tissue were evaluated via immunohistochemistry.Fox P3, IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting.RESULTS: IL-17, IL-23, IL-8, IL-33, TNF-α, and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups. Conversely, Treg cell and Fox P3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups. The IL-23/IL-17 A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells, leading to reduced Fox P3 levels and mediating the loss of tolerance in PBC.CONCLUSION: DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17 A signaling pathway expression and upregulating Fox P3 expression.