OBJECTIVE: To investigate efficacy of Lidan Tang (LDT) on gallstone induced by high fat diet in mice, and to study its underlying mechanism. METHODS: Mice were fed with high fat diet every day and treated with LDT (9.01 times of human clinic dosage). Mice were randomly divided into 6 groups as control group, gallstone model group (high-fat diet), positive control ursodeoxycholic acid (UDCA) group (80 mg.kg(-1).d(-1) i.g.), LDT low dose group (6 kg/d, i.g.), LDT middle dose group (12 kg/d, i.g.), and LDT high dose group (24 kg/d, i. g.). The whole experiment was lasted for 4 weeks. The levels of ALT, AST, LDH, CHO, HDL-C and LDL-C in serum were measured, the pathological sections were observed by hematoxylin-eosin staining, the activities of antioxidant enzymes were measured by kits, and the proteins related to oxidative stress and lipid transport were detected by Western blot analysis. RESULTS: LDT could significantly reduce the contents of ALT and AST in serum and improve the pathological tissue of liver. LDT could significantly reduce the content of MDA and LPO, and increase the level of GSH and GSH-PX in liver tissue. The data of Western blot showed that LDT had antioxidant effect promoting Keap1/Nrf2 pathway and regulated the process of lipid transport, which was statistically significant. In addition, LDT treatment inhibited the expression of ATP-binding cassette transports ABCG5/8 in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. CONCLUSION: LDT has protective effect on gallstones induced by high fat diet in mice, which might be based on the protective effect on liver, including enhancing the antioxidant capacity of liver and reducing the production of lipid peroxides. (C) 2020 JTCM. All rights reserved.