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The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot analysis. Enzymatic activity of MMP-12 was determined by β-casein zymogra-phy. RT-PCR analysis was used to measure the mRNA expression level of MMP-12. OxLDL-stimulated macrophages produced increased casein-degrading activities and oxLDL also significantly increased the mRNA level of MMP-12 in a dose-dependent manner. OxLDL stimulated the phosphorylation of ERK1/2 in macrophages. The use of the specific inhibitor indicated that the ERK1/2 signaling pathway was required for the induction of MMP-12. These data demonstrated that oxLDL induced MMP-12 expression in macrophages through an ERK1/2-dependent pathway.