Numerous reports have confirmed the effect of ApoE knockout in the induction of cardiovascular diseases and the protective effect of adiponectin against the progression of cardiovascular diseases. The aim of this study was to reveal the roles of adiponectin signaling in the progression of cardiovascular diseases induced by ApoE knockout and to analyze the healthy effects of aerobic exercise on ApoE knockout mice (ApoE^-/- mice) through observing the changes of adiponectin signaling caused by ApoE knockout and aerobic exercise. A twelve-week aerobic exercise program was carried out on the male ApoE^-/- mice and the C57BL / 6J mice (C57 mice) of the same strain. Results show that the body weights, blood lipid level, plasma adiponectin level and adiponectin-related proteins in myocardial tissue were all significantly changed by ApoE knockout. A twelve-week aerobic exercise program exerted only minimal effects on the body weights, blood lipid levels, and plasma adiponectin levels of ApoE^-/- mice, but increased the expressions of four adiponectin-related proteins, AdipoR1, PPARα, AMPK and P-AMPK, in the myocardial tissue of the ApoE^-/- mice. In summary, adiponectin signaling may play an import role in the progression of cardiovascular diseases induced by ApoE knockout, and the beneficial health effects of aerobic exercise on ApoE^-/- mice may be mainly from the increased adiponectin-related protein expression in myocardial tissue.

• A twelve-week aerobic exercise program exerted only limited effects on the body weights and the plasma adiponectin levels of both the normal mice and the ApoE^-/- mice but did effectively regulate the blood lipid levels of the normal mice (but not the ApoE^-/- mice).

• After 12 weeks of aerobic exercise, expression of the adiponectin-related proteins in the myocardial tissue of the ApoE^-/- and normal mice was increased, but the increased amplitudes of these proteins in the ApoE^-/- mice were much larger in the ApoE^-/- mice than in the normal mice.

• Aerobic exercise might not alter the plasma adiponectin levels and blood lipid levels of ApoE^-/- mice, but improve myocardial energy metabolism and relieve cardiovascular disease symptoms by increasing adiponectin-related protein expression in myocardial tissue.