Abstract: Objective To investigate the effects and mechanisms of apolipoprotein A-I mimetic peptides L-4F improving cardiac and coronary dysfunction in diabetic mice. Methods Twenty C57BL/6J mice were divided into control group(n=10)and control + L-4F group(n=10), twenty db/db mice were divided into diabetic group(n=10)and diabetic + L-4F(n=10).Mice were treated with either L-4F or vehicle for 8 weeks, blood samples of glucose, insulin and adiponectin were measured in each group.The isolated hearts were prepared to measure the cardiac and coronary functions.Western blot analysis of cardiac tissue for heme oxygenase-1(HO-1), AMPK, pAMPK, peNOS, eNOS and iNOS was performed. Results Compared with diabetic group, levels of blood glucose, insulin, inflammatory cytokines in L-4F treatment group decreased significantly(P＜0.05), while adiponectin levels and left ventricular fractional shortening(LVFS)increased significantly(P＜0.05), and left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVESD)significantly decreased.Cardiac expression of HO-1, pAMPK and peNOS significantly increased(P＜0.05), while iNOS expression and peroxide levels decreased significantly(P＜0.05), and the coronary resistance(CR)also decreased significantly. Conclusion L-4F can upregulate the expression levels of HO-1, adiponectin, pAMPK and peNOS, increase levels of anti-oxidative, anti-inflammatory and improve endothelial function, which will prevent myocardial and coronary dysfunctions in db / db mice.