Abstract: Objective To observe the expression pattern of peroxisome proliferators-activated receptor-γcoactivator-1α(PGC-1α) and mitofusin 2 (Mfn2) in insulin resistance and recovery. To observe the changes of mitochondrial shapes and parameters in these conditions. Methods Adult Wistar rats were divided into normal control (NC) group, high-fat diet (HF) group and high-fat diet plus rosiglitazone maleate tablets (HF+RSG) group. Insulin sensitivity was tested by conscious hyperinsulinemic-euglycemic clamp at the end of the 4th and 8th week. At the end of 8th week, the expression level of PGC-1αand Mfn2 in skeletal muscle was measured by real time quantitative PCR and Western blot. Mitochondrial shape was observed by transmission electron microscope, and the mitochondrial parameters were analyzed by Image-Pro Plus 6 software. Results The insulin resistance formed in HF and HF+RSG group after 4 weeks high-fat diet. After another 4 weeks, the insulin resistance was recovered obviously in HF+RSG group because of feeding rosiglitazone maleate tablets. The expression of PGC-1αand Mfn2 decreased in HF group, significantly different from NC group. The expression of the two gene increased in HF+RSG group, significantly different from HF group. But compared with NC group, the expression of PGC-1αhad no significant difference. The expression of Mfn2 was still lower and significantly different from NC group. The mitochondrial shape and parameters had obvious changes in HF group. Conclusions The insulin resistance is relevant with the decrease of PGC-1αand Mfn2 expression, and also involve changes of mitochondria.