Objective To investigate the protective effects of aerobic exercise and miR-222 expression in myocardium of diabetic mice. Methods C57BL/6 mice were divided into 4 groups: normal non-exercise group(SC), normal exercise group(EC), non-exercise diabetic group(SD), and exercise diabetic group(ED). After the diabetic model was established successfully, EC and ED underwent a swimming training for 5 weeks. By the end of the experiment, light microscope was used to observe the pathological changes of heart, RT-PCR for myocardial miR-222 expression, and Western blot for phosphatase and tensin homolog deleted on chromosome ten(PTEN), phosphatidylinositol 3-kinase(PI3K), and protein kinase B(Akt)protein expressions in myocardial tissue. Results (1)Under the light microscope, the diabetic mice had a significant change in myocardial structure, with great disorder in the cell arrangement. After exercise intervention, the lesion was alleviated.(2)MiR-222 expression was increased in the myocardium of normal mice and DM mice after exercise(all P<0.05); (3)Compared with SC group, PTEN expression was increased and PI3K/Akt expressions were inhibited in myocardium of diabetic mice(all P<0.05). After exercise intervention, the expression of PTEN reduced(P<0.05)and PI3K/Akt pathway was reactivated in myocardium of diabetic mice(all P<0.05). Conclusion Exercise intervention may protect the myocardium under high glucose via inducing miR-222 and activating PI3K/Akt signaling pathway. (Chin J Endocrinol Metab, 2017, 33: 56-61) Key words: Exercise; miR-222; Diabetes mellitus; Myocardial protection