This study was carried on four groups of Wistar male rats (20 of each), to evaluate the protective ef- fect of vitamin E and selenium on the structure and biochemical al- terations of the liver, heart and aorta. Group I is control, Group II fed high fat and vitamin E and selenium deficient diet as control positive group. Group III (protective) given 100 mg and 0.1 mg/kg b.w/day for 6months, vitamin E and selenium respectively with high fat diet. Group IV were injected intra peritoneal Vit- amin E and selenium 1 g/100 g b.w for 6 months after feeding high fat diet for 6 months. At the end of experimental design, histological section from liver, heart and aorta and so serum changes in metabolites of heart and liver were exam- ined. The tissues of the control positive group showed accumulation of small and large fat globules in the hepatocytes, loss of striation in the cardiac muscles and thickening in the wall of the aorta with loss of the elasticity of the elastic membranes in the tunica media. While the addition of vitamin E and selenium (vitamin E 100mg. kg/bw and selenium 0.1mg. kg/b.w) to the ration of the third group (protective group), prevent the severe hazard effect that occurred in the second (control positive group).The injections of vitamin E and selenium 1ug/100g for 6 months lead to decrease the degenerative changes in the heart, liver and aorta with regeneration of these cells. Vitamin E and selenium administered or injected to Wistar rats decreased significantly the increase in serum levels of LDL, CPK, GOT induced by feeding high fat diet alone. These results collectively showed the beneficial effect of vitamin E and selenium as protective antioxidant to cardiac and liver biohazards induced by high fat diet and can be used as protective and therapeutically factor in liver, heart and blood vessels diseases. So, it's preferable to add vitamin E and selenium to the food in appropriate ratio to avoid the hazard effect of their deficiency, as protective treatment for liver, heart and blood vessels diseases.v