Atherosclerosis is the primary underlying pathology of CVD. Dietary treatment may be considered as one of the initial steps in the prevention of atherosclerosis. Replacing refined carbohydrate source of a cholesterol- enriched diet with antioxidant rich whole grain and inclusion of phytonutrition in the diet such as wild rice and phytosterols may reduce cardiovascular risk factors. The wild rice (Zizania palustris L.), an annual plant native to aquatic areas of the northern America, receives much attention by researchers because of its potent nutritional and phytochemical contents. Furthermore, another dietary component with cardiovascular benefits is the inclusion of plant sterols in our daily diet. The aim of this study was to investigate the antiatherogenic activity of wild rice in combination with phytosterols in LDL-r-KO mice. Male LDL-r-KO mice were divided into 4 groups receiving one of the following experimental diets for 20 weeks: 1. Atherogenic diet, 2.Wild rice (as the main source of dietary carbohydrates) diet, 3. 2% Phytosterols-enriched diet and 4. Diet containing both wild rice and 2 % phytosterols. Blood samples were collected through jugular vein during study, and at sacrifice through cardiac puncture; the heart and fecal materials were collected and used for biochemical and histological examinations. The supplementation of wild rice in combination with phytosterols to an atherogenic diet for up to 20 weeks significantly reduced the total plasma concentrations of cholesterol (TC) in LDLr-KO mice. However, there was no significant difference in triglyceride (TG) in wild rice in combination with phytosterols after 20 week exposure of diet. Further, wild rice in combination with phytosterols resulted in increased fecal excretion of cholesterol. Also, there was reduction in the development of atherosclerotic lesion in the group of mice supplemented with wild rice in combination with 2% phytosterols (w/w). Our data support that combination of plant sterols and wild rice does not have additive effect in lowering cardiovascular risk.