A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs). Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n= 8), enalapril (an ACEI, 10mg· kg-1· day-1) alone (n= 8), curcumin (50mg· kg-1· day-1) alone (n= 9) and enalapril plus curcumin (n= 9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0±1.9%) and curcumin (30.8±1.7%) groups than in the vehicle group (19.7±1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4±1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group. A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats.(Circ J 2011; 75: 2151-2159)