Abstract INTRODUCTION: Peroxidation of blood lipoproteins is regarded as a key event in the development of atherosclerosis. Evidence suggests that oxidative modification of amino acids in low-density lipoprotein (LDL) particles leads to its convert into an atherogenic form, which is taken up by macrophages. Therefore the reduction of oxidative modification of lipoproteins by increasing plasma antioxidant capacity may prevent cardiovascular disease. methods: In this study, the antioxidant and anti-fatty streak effects of L-serine were investigated in hypercholesterolemic rabbits. Rabbits were randomly divided into three groups which were fed high-cholesterol diet (hypercholesterolemic control group), high-cholesterol + L-serine diet (treatment group), and normal diet (control) for twelve weeks and then blood samples were obtained to measure plasma cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), antioxidant capacity (AC), malondialdehyde (MDA), and conjugated dienes (CDS). Right and left coronary arteries were also obtained for histological evaluation. results: No significant difference was observed in plasma cholesterol, TG, HDL, LDL and CDS levels between treatment and hypercholesterolemic control groups (P>0.05). The levels of plasma MDA and AC were 0.29 µM and 56%, respectively in the treatment group which showed a significant change in comparison with hypercholesterolemic control groups (P<0.05). The mean size of produced fatty streak also showed significant reduction in the treatment group compared to the hypercholesterolemic group (P<0.05). CONCLUSIONS: The results showed that L-serine has antioxidant and anti-fatty streak effects without any influence on plasma lipid levels in hypercholesterolemic rabbits. Keywords: Atherosclerosis, cholesterol, L-serine, antioxidant, lipids, fatty streak.