In this study, we employed an homozygous db/db and heterozygous mice in vivo to determine 1) if irisin treatment could increase the resistance of the mice to development of myocardial dysfunction and remodeling; 2) Whether irisin treatment prevents cardiac remodeling and attenuate insulin resistance; 3)Whether irisin-induced physiological function is associated with p38 mitogen-activated protein kinase (MAPK) and HDAC4 in db/db mice. The gene discussed is FNDC5; the disease is Insulin resistance.