Our study indicates that p21WAF1 might regulate the p38MAPK signaling pathway via MMP-9 expression by inducing the binding activity of the Sp-1 motif in controlling the migration and invasion of IL-16-stimulated VSMCs, which leads to the formation of vascular lesions in vascular diseases such as atherosclerosis and restenosis. This evidence concerns the gene MMP9 and atherosclerosis.