ObjectiveTo investigate the ameliorating effect of Xiao Chaihutang combined with Erchen Tang （XAE） on metabolic-associated fatty liver disease （MAFLD） in mice and the influence of this therapy on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/peroxisome proliferator-activated receptor α （PPARα） signaling pathway. MethodsForty-eight C57BL/6 mice were randomized into six groups： normal （CHOW）， atorvastatin （ATO， 0.05 g·kg^-1）， high-fat diet （HFD）， low-dose XAE （XAE-L， 10 g·kg^-1）， medium-dose XAE （XAE-M， 20 g·kg^-1）， and high-dose XAE （XAE-H， 40 g·kg^-1）. Each group contained 8 mice. Except the CHOW group， the other groups of mice were fed a HFD for the modeling of MAFLD. The experiment lasted for 20 weeks. Starting from the 13th week， mice were administered corresponding agents daily by gavage， and the mice in both the CHOW and HFD groups received equal volumes of purified water. At the end of the experiment， cardiac blood， liver， and adipose tissue samples were collected. Pathological staining was performed on the liver and adipose tissue separately. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglycerides （TG）， and total cholesterol （TC） in the serum， as well as TG and TC in the liver， were determined. Additionally， the mRNA levels of fatty acid synthetase （FASN）， stearoyl-CoA desaturase 1 （SCD1）， sterol regulatory element-binding protein 1c （SREBP-1c）， SIRT1， PPARα， PGC-1α， interleukin 6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the liver were measured by real-time PCR. The protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the mouse liver tissue were determined by Western blot. ResultsCompared with the CHOW group， the HFD group exhibited increased body weight， liver weight， and white adipose tissue weight （P<0.01）. After XAE intervention， these parameters were reduced compared with those in the HFD group （P<0.01）. Pathological section results showed that the morphology of hepatocytes and epididymal white adipocytes in the model mice was significantly improved after XAE intervention， with decreases in both the number and volume of lipid droplets. Furthermore， the XAE groups had lower levels of AST， ALT， HDL-C， LDL-C， TG， and TC in the serum and TG and TC in the liver than the HFD group （P<0.05，P<0.01）. Moreover， XAE administration downregulated the mRNA levels of lipid synthesis-related genes （FASN and SCD1） （P<0.05） and upregulated the mRNA levels of lipid oxidation-related genes （SIRT1， PPARα， and PGC-1α） （P<0.05，P<0.01）. Additionally， the protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the liver were upregulated after XAE treatment compared with those in the HFD group （P<0.05，P<0.01）. ConclusionXAE exerts a therapeutic effect on MAFLD by activating the SIRT1/PGC-1α/PPARα signaling pathway.