The skeletal muscles in animal models with metabolic syndrome and lifestyle-related diseases, e.g., type 2 diabetes, have decreased oxidative capacity, which is associated with reduced expression levels of the gene for peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Running restores decreased oxidative capacity in the skeletal muscles of rats with metabolic syndrome and type 2 diabetes, and hypertriglyceridemia and hyperglycemia are improved, respectively. Longer running distances are associated with increased oxidative capacity and PGC-1α mRNA levels in the skeletal muscles of rats with metabolic syndrome and type 2 diabetes. In contrast, a high-fat diet reduces the muscle oxidative capacity and PGC-1α mRNA levels of rats with metabolic syndrome, and weight gain, hypertriglyceridemia, and hyperglycemia are accelerated. Recently, mild hyperbaric oxygen at 1.25 atmospheres absolute with 36% oxygen has been proven effective for hypertension and type 2 diabetes. Mild hyperbaric oxygen inhibits a growth-related increase in glucose levels and further decreases high glucose levels in adult rats with type 2 diabetes-changes that are associated with improvements in muscle oxidative capacity and PGC-1α mRNA levels. This paper is a review of the fiber type distribution, oxidative enzyme activity, mRNA levels, and capillary architecture of skeletal muscles in animal models with metabolic syndrome and lifestyle-related diseases. In addition, the effects of a high-fat diet, exercise, and mild hyperbaric oxygen have been summarized.