Cardiovascular disorders in cancer patients with cachexia have recently become a great concern. However, the relationship between cancer cachexia and cardiac dysfunction remains unclear, due to lack of suitable models. We have established a novel murine model of cancer cachexia by implantation of human stomach cancer cell line 85As2, which represents impaired myocardial function in addition to anorexia and loss of weight and fat-free mass, which are similar to those observed in cancer cachexia patients. In this study, we investigated effects of voluntary wheel running (VWR) on cachexia-induced cardiac dysfunction, and myocardial gene expression using this model. VWR starting from 2 to 6 wks after implantation significantly suppressed the loss of heart and skeletal muscle weight as well as general symptoms of cachexia. Moreover, left ventricular ejection fraction significantly increased in cachexia group with VWR, compared to those without VWR. Microarray analysis revealed that the gene expression of an enzyme belonging to E3 ubiquitin ligase increased in the myocardium of cachexia mice, whose relation to skeletal muscular atrophy has not been reported. This suggests that the mechanism of myocardial impairment may be different from that of skeletal muscle atrophy. The present study indicates that VWR may improve not only cachexia symptoms but also cachexia-induced cardiac dysfunction. Further detailed studies are needed in order to examine the effect of VMR on myocardial gene expression, which may lead to establish an exercise therapy on cardiac dysfunction in cancer patients associated with cancer cachexia.