Aim To study the possible mechanisms of folic acid on hyperhomocysteinemia. Methods Rabbit aorta endothelial cell (EC) were isolated and cultured, then divided into six groups after adding native rabbit low density lipoprotein (nLDL) into the EC medium: control group (without any more agents added), folic acid group, tetrahydrobiopterin (BH 4)group, homocysteine (Hcy)group, folic acid plus Hcy group and BH 4 plus Hcy group. The following items were determined that is ① the degree of lipid peroxidation, ② the amounts of NO 2ˉ/NO 3ˉ, and ③ the activity of NO synthase (NOS). Results Folic acid plus Hcy group were similar with BH4 plus Hcy group. The various effects of Hcy were antagonized in both groups.Compare with Hcy group, the degree of lipid peroxidation significantly decreased (p<0.01), the amounts of NO significantly increased (p<0.01). The activity of NOS also increased (++). Conclusion There were same effects both folic acid and BH4. They may inhibit the co-injure of Hcy and LDL on EC by protecting effects of NO system.