Upregulation of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) by macrophages leads to atherosclerotic plaque rupture by degradation of the extracellular matrix. NF-κB activation regulates many key inflammatory genes linked to atherosclerosis. In the present study, the function of berberine, a natural extract from Rhizoma coptidis, on MMP-9 and EMMPRIN expression, the role of NF-κB activation in oxLDL-stimulated macrophages, and the possible mechanism in which NF-κB activation is involved were investigated. Berberine inhibited the expression of MMP-9 and EMMPRIN at both mRNA and protein levels. The phosphorylation of IκB-α and nuclear translocation of p65 protein were reduced by berberine, suggesting that NF-κB activation was inhibited by berberine in oxLDL-stimulated macrophages. Overall, berberine suppressed the expression of MMP-9 and EMMPRIN by at least reducing partly the activity of NF-κB in oxLDL-induced macrophages. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.