Aim Hyperhomocysteinemia is an independent risk factor for atherosclerosis (As). The mechanisms through which homocysteine (Hcy) results in As have not been fully understood. For investigation of these mechanisms, the effects of Hcy on lipid peroxidation, the injuries of Hcy to endothelium and its nitric oxide (NO) system were examined. Methods Rabbit aorta endothelial cell (EC) were isolated and cultured, then divided into seven groups immediately after adding native rabbit low density lipoprotein (nLDL) into the EC medium: ①control group of without any more agents added; ②folic acid group; ③tetrahydrobiopterin (BH4 )group; ④SIN-1 group; ⑤Hcy group; ⑥Hcy plus folic acid group; ⑦Hcy plus BH4 group. All groups were then incubated more 24 hours, and the following items were determined: ① The observation of morphology; ②The Content of malondialdehyde (MDA); ③The content of NO - 2/NO - 3; ④NO synthase (NOS) histochemistry staining. Results Hcy had strong effects on lipid peroxidation. The amount of MDA in Hcy group was much higher than the ones in other groups(P<0.01), the morphological appearance of EC had also corresponding changes; the formazan granules which imply the activity of NOS within EC was found dispersion on the EC surface out of the cells; and the production of NO - 2/NO - 3has yet decreased. The various effects of Hcy were partially antagonized by folic acid or BH4 adding: the production of MDA decreased, the amount of NO - 2/NO - 3increased, the activity of NOS and the morphological appearance of EC were preserved better. Conclusion Hcy showed strong effects on lipid peroxidation and EC injury which were involved the injurious effects of Hcy on NO system of EC. The protective agents of NO system showed alleviative roles against these injuries. Our results did not support that the autoxidation of Hcy, which has been suggested to produce H 2O 2, resulted in the lipid peroxidation and EC injury. The therapeutical mechanisms of folic acid on hyperhomocysteinemia may also involve the protection of NO system. 还原