Aim To evaluate the effects of inhibition of CD40-CD40 ligand system on development of atherosclerosis and the stability of lesions. Methods Eighteen male apolipoprotein E gene knockout mice were divided into positive control group(n=10) and anti-CD40 ligand antibody group(n=8).Serum lipids,soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1 were deteced.The aortas were taken for histomorphometry observation.The positive percentage of macrophage cells,smooth muscle cells and CD4~+T cells were determined by immunohistochemistry,and the expression of matrix metalloproteinase-9 were mesurated by Western blotting. Results Anti-CD40 ligand treatment could lower the levels of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1(p<0.01).It had no impact on serum lipids(p<0.05).Compared with positive control group,anti-CD40 ligand group showed a reduction in plaque area,plaque/intima size ratio,vascular thickness(p<0.05).Inhibition CD40-CD40 ligand also could reduce the amount of macrophage cells and CD4~+T cells,increase the amount of smooth muscle cells(p<0.05).The expression of matrix metalloproteinase-9 decreased in anti-CD40 ligand antibody group(p<0.01). Conclusions Inhibition of CD40-CD40 ligand could decrease vascular inflammation,prevent development of atherosclerosis.It had no impact on serum lipids.