Objective To investigate the effect of the Chinese medicine Jinlida on triglyceride-related genes in skeletal muscle of fat-induced insulin resistant ApoE^-/- mice. Methods Eight male C57BL/6J mice were set to the normal group (group A). Forty male ApoE^-/- mice were fed high-fat diet for 16 weeks and divided into model group (group B), rosiglitazone (group C), Jinlida low dose group (group D), Jinlida moderate dose group (group E), Jinlida high-dose group (group F), and giving gavage for 8 weeks. TG content in the skeletal muscle was determined by enzymatic and BCA protein concentration assay. Oral glucose tolerance test (OGTT) was used to evaluate the degree of insulin resistance in the mice. Real-time fluorescent quantitative reverse transcription PCR (RT-PCR) and Western blot method were used to determine the expressions of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and proteins in the skeletal muscle. Results Jinlida to varying degrees lowered the fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), increased the high density lipoprotein (HDL-C), reduced fasting insulin (FIns) level and raised insulin sensitive index (ISI), and significantly improved the abnormal glucose tolerance in the mice. Jinlida to a certain degree raised the levels of HSL, ATGL, PPARγ mRNA and protein expressions. Conclusions Jinlida can alleviate fat-induced insulin resistance in ApoE^-/-mice through regulation of triglyceride-related gene expression.