Pomegranate is an important source of bioactive compounds that has been used for usual consumption as well as folk medicine for many centuries. This fruit contains high amount of phenolic compound with health benefits such as antioxidant, anticancer, and neutraceutical properties. The antiatherogenic properties of pomegranate has been also attributed to its capacity to decrease oxidative stress, the hallmark of early atherogenesis. Anthocyanins, a subgroup of flavnoids of phenolic are known to be responsible for the pomegranate peel and flesh color. It has been shown that antioxidants increase number of EPCs and contribute to the attenuation of atherosclerosis plaque size The object of this project was the effect of pomegranate peel anthocyanins on atherosclerosis plaque formation and plaque proteomics analysis. The anthocyanins of pomegranate peel were extracted using aciditic ethanol. Total polyphenolic compounds were determined 90.14 µg/µl according to the Folin-Ciocalteu procedure. Antioxidant activity of extract was determined using DDPH system and this extract shows 50% antioxidant activity in 3 microgram. Rabbits were assigned in 3 groups by standard diet, 1% high-cholesterol diet (HC group, n=6), or high-cholesterol diet with oral administration of an anthocyanin rich extract from pomegranate skin(HC+Pom group, n=6) for 8 weeks. Atherosclerotic plaque size was significantly reduced in anthocyanin fed rabbits in comparison to the control group and in threated group calcification was not observed. Alteration of MMPs was analyzed by gelatine zymography. The result of zymography shows increasing amount of MMP2 and MMP9 in cholesterol group in comparision to treated group and negative control. EPC (CD34+VEGF-R2+) circulating levels were evaluated in peripheral blood by Flowcytometry. CD34+ /KDR+ cells were significantly higher in treated group than cholesterol group (9.95±1.6 vs. 3.6±2.2, p 0.05). By the end of this research we studied the difference of aorta proteins between tree groups with two-dimentional electrophoresis and important difference between negative group and two other groups was observed. In this study for the first time beneficial consequence of pomegranate skin anthocyanins in prevention of this disease was reported. Dramatic alterations in the protein expression profile of aorta tissue was detected after the development of AS disease in rabbits. Investigationof the relationship between the differentially expressed proteins andthe initiation and development of the AS would be crucial for theunderstanding of the mechanism(s) of the disease and possible discovery of novel diagnosis markers and therapeutic approaches. Key words: Pomegranat, Antioxidant, Anthocyanin, Atherosclerosis, Proteomics