Aim To investigate the changes of aortic nitric oxide (NO) and NO synthases (cNOS and iNOS) in atherosclerotic rabbits induced by high cholesterol diet and the antiatherosclerotic effect of L-arginine. Methods Male New Zealand white rabbits were divided into three groups in random: the rabbits received either normal rabbit chow (normal group),1% cholesterol diet only (cholesterol group) or 1% cholesterol diet plus L-arginine (22.5% in drinking water, arginine group). Serum total cholesterol (TC), plasma L-arginine, asymmetric dimethlarginine (ADMA) and oxidized low density lipoprotein (ox-LDL) concentrations were detected. After 10 weeks, the aorta were harvested for assessment of NO production, NOS activities and area of intimal lesions. Results Compared with normal group, plasma L-arginine level had no significant alteration in cholesterol group, but serum TC, plasma ADMA and ox-LDL concentrations elevated markedly (P<0.01 orP<0.05). Aortic cNOS activity and NO production decreased about 45% and 30% respectively (P<0.01). Intimal lesions increased to 42.6%±9.2%. Compared with cholesterol group, dietary L-arginine had no effects on serum TC,plasma ADMA and ox-LDLconcentrations, but plasma L-arginine level increased about one time、aortic cNOS activity and NO production increased significantly (P<0.01). Intima lesion formation were inhibited markedly (19.5%±7.4% vs 42.6%±9.2%,P<0.05). Conclusions The activity of aortic NOS-NO system is impaired significantly in atherosclerotic rabbits induced by cholesterol diet. Progressive intimal lesion formation is associated with impaired activity of NOS-NO system. Decrease of cNOS activity results in reduction of NO production. L-arginine inhibits atherosclerotic progression by augmenting cNOS activity and restoring NO elaboration.