Objective: PGC1a is a key regulator of energy metabolism. Various factors are required for the regulation of muscle cell differentiation. In an attempt to elucidate the mechanism underlying myogenesis, we examined the possible contribution of mitochondria to terminal differentiation of murine myoblast cell line. Methods: These experiments were conducted with C2C12 cells. These myoblasts were infected with adenovirus containing PGC1a-GFP. We measured cellular mitochondrial proliferation, intracellular ATP concentration and mitochondrial mRNA and protein levels. Results: Within 2-3 days of serum starvation, myotubes began to form. The ratio of mitochondrial DNA to nuclear DNA increased time-dependently after differentiation induction. This suggests that the increase in mitochondrial DNA level exceeds the increase in nuclear DNA in accordance with the proliferation of cells, and that mitochondrial DNA accumulates in differentiating C2C12 myocytes. During differentiation, mRNA levels of MyoD, MHC, COX I, cytochrome b, AIF, and PGC1a and protein levels of aMHC, troponin T, electron transport chain complex I, cytochrome C, cytochrome c oxidase IV, and AIF were increased time-dependently. The levels of mRNA and protein were increased in AdPGC1a-treated cells, but decreased in SiRNA-PGC1a-treated cells. Conclusion: We have shown that the alterations of mitochondria change the myoblast differentiation into myotubes. PGC1a stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue.