Objective: It has become increasingly evident that significant alterations in the structure and composition of the extracellular matrix (ECM) play a key role in the atherogenic process. In the cardiovascular disease, an imbalance in matrix metalloproteinases (MMPs) may result in atherogenic progression from matrix degradation. Inhibition of endothelial dysfunction and matrix remodeling contributes to the attenuation of atherosclerotic lesion. Evidence suggests that nutritional antioxidants can contribute to the prevention of atherosclerosis by reduction of gelatinases activity. The goal of the present study was to determine whether such beneficial effects of pomegranate peel antioxidant extract exist when supplemented to rabbits feeding a high cholesterol diet. Materials and Methods: Gelatinases activity was detected by gelatine zymography and rabbit atherosclerotic lesion size were determined by hemotoxin and eosin staining method in rabbits feeding normal diet, high-cholesterol diet and high-cholesterol diet with pom(0.1% in drinking water) after 2 months. Results: Pom supplementation significantly decreased pro and active MMP9 activity in pom group than cholesterol group . In hypercholesterol group(but not two other groups) an additional gelatinolytic band at 72 kD was evident, corresponding to MMP-2 activity. Atherosclerotic lesions of abdominal aorta rabbits significantly reduced in the pom group (p<0.03). Our results suggest that the beneficial effect of pomegranate peel antioxidant extract in prevention of atherosclerosis may be due to the modulation of gelatinases activity that could be a potent therapeutic strategy. Conclusion: In this study for the first time beneficial effects of pomegranate skin anthocyanins in reduction of gelatinases activity and attenuation of atherosclerotic lesion was reported.