Hypercholesterolemia is one of the major risk factors that precipitate coronary heart disease andatherosclerosis. In the present study, the effect of flaxseed oil supplementation on serum lipid profile,apolipoprotein A (apo A), apolipoprotein B (apo B), Lipoprotein a Lp(a), homocysteine and endotheline-1(ET-1) in high cholesterol diet-induced hypercholesterolemia in rats have been evaluated. This study wascarried out on 60 male rats. The rats were divided into four equal groups of 15 rats each. Group ? :( Controlgroup): rats fed on normal diet. Group ?: Rats fed with hypercholesterolemic diet (HCD) [4% cholesterol(w/w) and 1% cholic acid] and received no drug all over the period of the experiment. Group III: Rats fedwith HCD administrated flaxseed oil (270 mg/kg, body weight/day orally) after two weeks from inductionof hypercholesterolemia. Group IV: Rats fed with normal diet administrated with flaxseed oil (270 mg/kg,body weight/day orally) after two weeks from the onset of the experiment. Blood samples were collectedfrom all animal groups three times at 2, 4 and 6 weeks from the onset of treatment with flaxseed oil. Theobtained results showed that, cholesterol-induced hypercholesterolemia caused a marked increase in serumtotal cholesterol, triacylglycerols, LDL-C, VLDL-C, phospholipids, lipoprotein A, Apo B, endothelin-1 andhomocysteine. On the other hand, a significant decrease in serum HDL�C and Apo A were observed in highcholesterol diet-induced hypercholesterolemia in rats. Treatment with flaxseed oil to high cholesterol dietinducedhypercholesterolemia rats lowered serum total cholesterol, triacylglycerols, LDL-C, VLDL-C,phospholipid, endothelin-1 and homocysteine concentration in addition to increasing HDL-C and Apo A.These results suggest that, flaxseed oil may be effective in controlling cholesterolemic status and improvingdyslipidemia and has the potential in reducing cardiovascular complications due to hypercholesterolemia.