Mapping on the human genome and genome of other organisms revealed not only the DNA organization principles, but also showed the regulation complexity of the structural and metabolic genes expression. It turned out that external influences such as nutrition, stress, physical activity and other external stimuli change genes expression and control it through a complex set of regulatory mechanisms. A complex set of molecular mechanisms, including genetic and epigenetic factors, is involved in the regulation of skeletal muscle metabolism. Epigenetic regulation of gene expression in human skeletal muscles is carried out at three levels: DNA methylation, histone modification and mRNA-microRNA interaction. The article considers the possible mechanisms of epigenetic regulation of intracellular metabolism of skeletal muscles during single and systematic exercises.