The effect of forced running for 1 hour daily for 4 weeks on the content of Na+/K+-ATPase isoforms and monovalent cations in the skeletal muscles of mice with a model of type II diabetes mellitus (DM-II) was studied. To form a model of the disease, a high-fat diet was used, and physical activity in the form of forced running was carried out for 4 weeks. The content of Na+/K+-ATPase isoforms and Na+ and K+ ions in muscle tissue of m. gastrocnemius was determined by Western blotting and atomic absorption spectrophotomery, respectively. It has been shown that the formation of DM-II in mice is accompanied by changes in the content of Na+/K+-ATPase alpha 1 and 2 isoforms in muscle tissue. The effect of forced running loads on the content of Na+/K+-ATPase in muscle tissue is significant and primarily differs in age groups. One can also note a certain dependence of the influence of forced running loads on the content of this enzyme on the time of their use. In young animals, changes in the concentrations of monovalent sodium and potassium cations after forced running loads were less pronounced. In aged mice, against the background of forced loads, an increase in the content of sodium and decrease in the content of potassium in muscle tissue was observed. The detected changes in monovalent cations content in the muscle tissue of mice with diabetes mellitus II under the influence of forced running loads may play a role in the implementation of the metabolic effects of physical activity.