Macrophage cholesterol and oxidized lipids accumulation and foam cell formation occur in the early stages of atherosclerosis development. In the current study we used the J774A.1 murine macrophage cell line in order to analyze two atherogenic functions: a. the ability of the cells to produce reactive oxygen species (ROS), and to increase cellular oxidative stress, and b. the ability of the cells to synthesize cholesterol, leading to cholesterol accumulation in the cells. The addition of punicalagin, or beta-sitosterol, or pomegranate juice (which contains both of the above) to simvastatin, significantly improved the statin's ability to inhibit macrophage cholesterol biosynthesis. Furthermore, the addition of pomegranate juice (or punicalagin, but not beta sitosterol) to simvastatin significantly increased the statin ability to protect the cells from oxidative stress. Taken together, the current research provides evidence for the additional cardio protection of statins, that is provided by pomegranate juice antioxidant and hypocholesterolemic effects. The use of statins in combination with pomegranate juice in hypercholesterolemic patients, may allow for the use of lower dosages of statin in order to prevent statin deleterious side effects.