Abstract Objective: To examine the effect of hypercholesterolemia (HC)on cardiac function in rabbit model. Design and method: 12 adult rabbits divided into 2 groups of 6 rabbits each:Control(C) fed on normal chow, and (HC) fed on 2% cholesterol (Iard mixed with chow) for 16 weeks. After treatment, rabbits from (C) and (HC) groups were sacrificed and hearts were quicky removed, and perfused with standard Krebs Hanseleit buffer at a rate of 10 ml/minute at 37°C, pH 74 in Langendorff retrograde perfusion system at a constant pressure.45 minutes ischemia was followed by 120 minutes reperfusion and parameters of cardiac function: coronary flow (HC), Heart rate (H.R.) and left ventricle developed pressure (LVDP) of hearts from (C) and (HC) groups were measured. TACS DNA laddering kit was used to assess left ventricle cardiomyocytes from group (HC) for apoptosis, also fragments of left ventricle from (HC) were processed for Electron Microscopy (EM). Results: Evaluation of (C.F.), (H.R.) and (LVDP) in (C) and (HC) groups have pointed out a 50% reduction in (C.F). in (HC) group versus (C) during stabilization period In (HC) group, LVDP was depressed during the whole experiment, while in (C) group is was almost constant. Protection of myocardium against oxidative stress was significantly depressed following (HC) treatment, synthesis and utilization of GSH was limited versus (C). Cardiac hypertrophy experimentally induced with (HC) was related with a decrease in (C.F.) and LVDP associated with an increase in lipid peroxidase, in LDH and CK as markers of myocardial lesion and GGT activity in myocardial tissue. Myocyte apoptosis was present in (HC) group, pointed out by DNA laddering pattern on gel electrophoresis. (E.M.) studies have pointed out perinuclear edema of myocytes, dilated sarcoplasmic reticulum and swollen mitochondria. Conclusions: High cholesterol diet in (HC) rabbits induces cardiac hypertrophy and changes in physiological parameters of heart with a negative impact upon synthesis of antioxidant enzymes as well as changes in ultrastructure of heart muscle and at the molecular level (DNA laddering is present as a sign of apoptosis in ventricular myocytes).