Aim To investigate the change rule and correlation of carbon monoxide (CO)/heme oxygenase-1 (HO-1) and nitric oxide (NO)/nitric oxide synthase (NOS) system in atherosclerosis and the influence of the two systems on atherosclerotic progress. Methods The rabbits received 1% cholesterol diet (chol group, n=8)or 1% cholesterol diet plus L-arginine (L-arg group, n=8) or L-NAME (L-NAME group, n=8) by drinking water, or 1% cholesterol diet plus heme-L-lysinate (Heme group, n=8) or ZnPP-IX (ZnPP group, n=8) by injection in abdominal cavity for ten weeks. Results Compared with contrast group, in chol group, aortic NO production and expression of NOS were decreased markedly; however, CO production and HO-1 activity were increased obviously (p<0.01). Compared with chol group (40.2%±8.9%), aortic plaque areas of heme group(26.6%±9.2%) was reduced distinctly while aortic CO production and NOS activity were increased obviously (p<0.01). However, compared with contrast group, HO-1 expression and CO production in heme group were decreased markedly (p<0.01) while they were not different from the chol group (p>0.05). Compared with chol group, aortic NOS activity and NO production of L-arg group were increased obviously and aortic plaques area (28.1%±7.7%) was reduced greatly (p< 0.01 ). HO-1 expression and CO production of L-arg group were increased distinctly compared with contrast group while they were not different from chol group (p>0.05). Compared with chol group, aortic c-myc and c-fos expression of both heme group and L-arg group were reduced markedly while in ZnPP and L-NAME group they were not different from chol group. Conclusions The reciprocal relationship between heme oxygenase/carbon monoxide and nitri coxide synthase/nitrogen monoxide system in atherosclerosis could play the inhibitory role against atherosclerotic lesion.