OBJECTIVE: To investigate the mechanism by which Daifan San (DFS) prevents and treats primary biliary cirrhosis (PBC) via the forkhead box P3 (FoxP3) and interleukin (IL)-23/IL-17A signaling pathways. METHODS: Ninety C57BL/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, type III collagen, cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry. FoxP3, 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-alpha, and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups. Conversely, Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups. The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells, leading to reduced FoxP3 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-17A signaling pathway expression and upregulating FoxP3 expression. (C) 2020 JTCM. All rights reserved.