AIM:To investigate whether ginsenoside Rg1 attenuates high-fat diet ( HFD)-induced non-alcoho-lic fatty liver disease ( NAFLD) by improving β-oxidation.METHODS: SD rats ( n=60) were randomly divided into control group ( CON ) , HFD group, low-dose, medium-dose and high-dose ginsenoside Rg1 groups ( LDG, MDG and HDG) and positive drug ( sodium ursodeoxycholate) treatment group ( PDT) .High-fat diet was given for 8 weeks to suc-cessfully establish an NAFLD model.The animals were treated with the appropriate medications for 4 weeks and 8 weeks af-ter modeling, and sacrificed to collect the liver tissues for observing the pathologic changes with HE staining and for detec-ting liver functions and lipid levels.The expression of hepatic acyl-CoA synthetase 1 (CoASH1), carnitine acyltransferase I (CATI) and acyl-CoA oxidase 1 (ACOX1) at mRNA and protein levels was determined by RT-PCR and Western blot-ting.RESULTS:After 4-week treatment, the fatty infiltration of the liver tissues in PDT group, LDG group and MDG group was not attenuated except HDG group.After 8 weeks of treatment, a small number of fat particles was observed in PDT group and LDG group, while no infiltration of lipid droplet was found in MDG group and HDG group.Compared with HFD group, the levels of AST, ALT, AKP, TC, TG and LDL-C were significantly decreased after 4-week treatment in PDT group, LDG group, MDG group and HDG group (P<0.05), these indexes were further reduced after 8-week treatment. After 4-week treatment, HDL-C was significantly increased in the 4 treatment groups and almost restored to the level of CON group after 8-week treatment.The levels of CoASH1, CACTI and ACOX1 in the liver tissue of the 4 treatment groups were significantly increased after 4-week treatment (P<0.05) and much improved after 8-week treatment, and those in MDG group and HDG group were better than those in PDT group (P<0.05).CONCLUSION:Ginsenoside Rg1 regulatesβ-oxidation-related enzymes to improve the fat metabolism, thus playing a therapeutic role in liver injury in the rats with NAFLD.