The extracellular matrix metalloproteinase inducer (EMMPRIN) is significant in the regulation of matrix metalloproteinase (MMP) synthesis in atherosclerosis-related cells, and is possibly involved in the progression of atherosclerotic plaque. EMMPRIN expression is also up-regulated in PMA-induced THP-1 cells and is inhibited by resveratrol. However, it remains unclear how resveratrol inhibits EMMPRIN expression. We thus investigated the role of the MAPK signaling pathway in resveratrol inhibiting the up-regulation of EMMPRIN in PMA-induced THP-1 cells. We found that the ERK1/2 and p38 pathways, but not the JNK, are activated during the up-regulation of EMMPRIN expression. We also observed that while resveratrol suppresses the up-regulation of EMMPRIN, it also suppresses both the ERK1/2 and p38 pathways in a dose-dependent manner. Taken together, we established that it is through both the ERK1/2 and p38 MAPK pathways that resveratrol inhibits the expression of EMMPRIN in PMA-induced THP-1 cells.