Aim To investigate the influence of carbon monoxide(CO)/heme oxygenase-1 (HO-1) system on neointimal proliferation and endothelium function. Methods Fifty rabbits were randomly divided into 5 groups of 10 rabbits. Control group received normal chow(C group),the other rabbits received 1.5% cholesterol diet (Ch group and SH group) or 1.5% cholesterol diet plus hemin (Hm group) or zincprotoporphyrin IX (Zn group) for 10 weeks. At the beginning of 3rth week,Ch group,Hm group and Zn group underwent balloon injury at one side carotid artery. Results High cholesterol diet markedly enhanced the levels of serum TC,TG,LDLC and ox-LDL (P><0.01). However,they were not much different among these four experimental groups. Compared with control group,arterial NO production and cNOS activity decreased markedly,while CO production and HO activity increased markedly(all P><0.01),the intima area and ratio of intima/media (I/M) were respectively 0.586±0.090 vs 1.381±0.180 in Ch group. Compared with Ch group,CO production and HO-1 activity increased markedly in Hm group,while in Zn group they were decreased markedly. Compared with Ch group,arterial endothelin-1(ET-1) level of Hm group reduced markedly while in Zn group they were significantly higher than Ch group. The intima area and ratio of I/M were reduced distinctly in Hm group (respectively 0.386±0.076 vs 0.862±0.164) while they were distinctly increased in Zn group (respectively 0.734±0.096 vs 1.843±0.212). Conclusion Arterial NOS/NO system is impaired significantly in atherosclerotic rabbits induced by highcholesterol diet and balloon injury.HO-1/CO system plays a key role in improving endothelium function and inhibiting neointimal proliferation. This role is related to the reciprocal relationship between HO-1/CO and NOS/NO system in restenosis and the down-regulated expression of ET-1.