Abstract： Objective To investigate the possible mechanisms of ox-LDL on vascular smooth muscle cells (VSMC) with and without exogenous zinc finger protein A20 gene. Methods VSMC were trans-fected with plamid containing A20 gene and incubated with ox-LDL. TLR4 and LOX-1 mRNA expression were measured by RT-PCR. Results After VSMC incubated with ox-LDL, the expression of LOX-1 and TLR-4 mRNA reached a higher level. However, when VSMC were transfected with plasmid containing A20 gene, the NF-kB nuclear translocation and the ability of migration reduced to normal level. Conclusions ox-LDL can significantly activate NF-kB signaling system and enhance migration in VSMC. The activation may induce the inflammatory response in arterial wall, the migration of VSMC to the intima, and triggering the process of atherosclerosis. Transfecting plasmid containing A20 gene significantly inhibited the activation of NF-kB and the ability of migration of VSMC. A20 effects might be through inhibiting NF-kB signaling. Meanwhile, A20 blocked the development of atherosclerosis.