The main proposal of this study was to evaluate in vivo whether flaxseed oils fortified with micronutrients would have beneficial effects on lipid profile and antioxidant status in high-fat fed rats. Male Wistar rats were fed synthetic diets containing 10% of flaxseed oil (FO), phytosterols (PS) fortified FO (PS-FO), vitamin E (V-E) fortified FO (V-E-FO), V-E, and PS fortified FO (V-E-PS-FO), respectively, for 4 wk. The results showed that V-E fortified FO enhanced the enzymatic (SOD and GPX) and nonenzymatic (GSH and V-E) antioxidant system, lowered the lipid peroxide (TBARS) concentration compared with FO (P < 0.05). And FO fortified with PS significantly reduced the plasma TG, TC and LDL-C levels, and hepatic TG and TC levels of rats compared with FO (P < 0.05), but had no significant effect on antioxidant defense capacities. Combined addition of V-E and PS in FO had a synergetic effect. These results indicated that flaxseed oils fortified micronutrients V-E and PS may contribute to reduce the risk factors of cardiovascular disease (CVD) by improving plasma antioxidant defenses and lipids profiles.