Objective In this study, the glucose and energy metabolism-related genes (PGC-1α, Glut-4, ERRα, NRF-1, TFAM and mtDNA gene) were detected in type 2 diabetes mellitus (T2DM) and non-T2DM minipigs, and the gene function was explored for T2DM pathogenesis. Methods The longissimus muscle of T2DM and non-T2DM Guangxi Bama mini-pigs was used as experiment material. The expression of glucose and energy metabolism-related genes was detected by QRT-PCR. Results The expressions of PGC-1α, Glut-4, ERRα and NRF-1 genes were significantly higher than that of non-T2DM group, the expressions of TFAM and mtDNA gene were lower than that of non-T2DM group. Conclusions The upregulated expression of PGC-1α gene and its downstream genes Glut-4, ERRα, NRF-1 may improve the glucose metabolic functions in skeletal muscle in the Bama minipigs, whereas insufficient mitochondrial synthesis may induce decreasing ATP synthesis, and results in skeletal muscle insulin resistance, finally leading to the T2DM occurrence.