Background: Atherosclerosis is a complex disease that is associated with a variety of etiologic factors such as hyperlipidemia and inflammation. Aloe vera (Liliaceae family) has been used traditionally as an anti-inflammatory drug. The aims of this survey were to define the beneficial effects of Aloe vera leaf gel on some of the atherosclerosis risk factors, and also fatty streak formation in hypercholesterolemic rabbits. Materials ans Methods: 32 white male rabbits were randomly divided into four experimental groups (n = 8, each). During the study, the animals had a standard diet (control group), high cholesterol diet (HC group), high cholesterol diet with Aloe vera leaf gel (3.2%v/v) (HC+ Aloe group) and Aloe vera leaf gel (Aloe group) for 30 days. Fasting blood samples were collected from all animals at the beginning and end of the study. Then total cholesterol (TC), fasting blood sugar (FBS), triglyceride (TG) and CRP were measured before and after experimental periods. By the end of the study, the aortas were removed and investigated for atherosclerosis plaque formation. Results: Significant differences were observed in TC and CRP levels of the high-cholesterol diet with Aloe vera and the high-cholesterol diet alone (p < 0.05). The formation of fatty streaks in the aorta was also significantly lower in the same animals under the influence of dietary Aloe vera(p < 0.05). The control and Aloe group did not show any evidence of atherosclerosis. No significant difference was found between the groups in TG and FBS. Conclusions: The data suggests that Aloe vera has beneficial effects on the prevention of fatty streak development; it may reduce the development of atherosclerosis through modification of risk factors. However, further studies are needed to understand the mechanisms whereby this plant exerts its anti-atherosclerotic effects.