ABSTRACT— The study was designed to investigate the effect of L-arginine on atherosclerosis particularly by identification of some elements of inflammatory and oxidative cascades. Eighteen local domestic rabbits (male) were introduced and allocated into 3 groups (6 rabbits per group) and the duration of the study was 12 weeks. The first one was considered as a negative control group in which animals received normal diet only. The second one was the group in which rabbits received dietenriched with cholesterol (5 %). The last group was the one in which received dietenriched with cholesterol (5 %) together with oral L-arginine (1.5%). At the end of the study, animals were sacrificed, and blood sampleswere to identify serumlevels endothelin-1(ET-1) and tumor necrosis factor-alpha (TNF-?). Lipid parameters (TC, TG, HDL-C, LDL-C and VLDL-C) were also determined in the serum. Aorta was isolated to detect total antioxidant capacity (TAC) and intimal thickness. Treatment of rabbit with L-arginine was associated withsignificant elevation of serum level of TC, HDL-C and LDL-C but insignificant reduction in TG and VLDL-C level when compared with untreated group. Treatment with L-arginine was associated withinsignificant elevation ofboth serum TNF-? level and aortic TAC andinsignificant reduction in serum ET-1andaortic intima thickness when compared with untreated rabbits. L-argininehas a potential ameliorating effect on atherosclerosis. This was mainly achieved by its inhibitory effects on some inflammatory and oxidative cascades.