AIM To create a novel mouse model of combined hyperlipidemia using a modeling agent (MA) made of a mixture of schisandrin B, cholesterol and bile salt (1,2 and 0.5 g·kg-1) suspended in olive oil 20 ml·kg-1.METHODS Mice were given a single dose of MA via intragastric garage.Blood biomarkers and hepatic lipids as well as hepatic weight were determined at 12, 24,48, 72, 96, or 120 h following the administration of MA.RESULTS Results showed that MA treatment increased serum triglyceride (TG) and total cholesterol (TC) (up to 422 and100% at 12-96 h post-treatment, respectively) and hepatic TG and TC (up to 220and 26% at 12-120 h post-treatment, respectively) in a time-and dose-dependent manner.Simultaneously, MA treatment elevated the serum high density lipoprotein and low density lipoprotein.Besides, serum alanine/aspartate aminotransferase and aspartate aminotransferase activity was elevated (up to 198 and 64%, respectively) at 48 and 72 h post-MA treatment.Hepatic index, were increased (up to 66%) at 24-120 h post-MA treatment.Fenofibrate pretreatment (0.1 g·kg-1 for 4 d) reduced serum TG and TC levels as well as hepatic TG content in MA-treated mice.However, the combined treatment with MA and fenofibrate showed an increase in liver weight (up to 139%) in an additive manner.CONCLUSION Oral administration of a mixture of schisandrin B, cholesterol and bile salt could generate an interesting mouse model of combined hyperlipidemia associated with hepatic steatosis and steatohepatitis.