Today, exercise is regarded as one of therapies for heart failure (HF). However, the effects of exercise on patients with dilated cardiomyopathy (DCM) have not been established. A knock-in mouse model of human inherited DCM, TNNT2 ΔK210, shows similar characteristics to DCM patients. We aimed to examine how the frequency of voluntary exercise influence progression of heart failure using the DCM model mice.Homozygous ΔK210 (DCM) mice showed enlarged heart and frequent sudden death with t1/2 of ～70 days. DCM mice were divided into 3 groups based on the frequency of voluntary exercise: no exercise control, every 2 days (2D) and daily exercise (ED). The 2D and ED groups started running at 1 month of age. At the 2 months of age, mice were sacrificed after an investigation with echocardiography, and their heart, lung, lower extremity muscles and body weights were measured. Gene expressions of HF- and arrhythmia-related genes in myocardium were quantified by qPCR analysis. The ejection fraction was significantly improved in ED group compared with 2D and control. ED group showed attenuated electrical remodeling in the hearts. These result indicated that daily voluntary exercise prevents progression of HF in DCM mice.