Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO 2 ) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO 2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO

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... 2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO 2 . STZinduced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO 2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO 2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.