BACKGROUND : HMG CoA reductase inhibitors (statins) significantly reduce the incidence of cardiovascular events. The hypothesis of this study is as follows; the treatment with statins may change the functional activity of circulating monocytes and directly modulate the expression levels of genes that affect the process of monocyte recruitment. RESULTS : The treatment of THP-1 monocytes with one of the representative statins, simvastatin, significantly reduced CCR2 (CC chemokine receptor 2) expression, the dominant chemokine receptor in monocytes. The amount of monocyte CCR2 transcripts and proteins was reduced by 50% after the treatment with simvastatin. When 21 healthy normocholesterolemic males were medicated with simvastatin (20 mg/day) for 2 weeks, the amount of monocyte CCR2 proteins and serum MCP-1 levels were significantly reduced, which were all returned to the basal levels after withdrawals of the medication for 2 weeks. The downregulatory effect of simvastatin on CCR2 expression was completely reversed by mevalonate and partially by geranylgeranylpyrophosphate (GGPP). The treatment with simvastatin induced PPAR activation in THP-1 monocytes and the downregulation of CCR2 expression induced by simvastatin was abolished by a synthetic PPAR inhibitor, . The treatment with simvastatin inhibited the MCP-1 (monocyte chemoattractant protein-1) mediated chemotaxis by 80 %, which were completely reversed by mevalonate. The medication of Sprague Dewerly rats with simvastatin (2 mg/kg for 2 weeks) decreased the interaction between circulating monocytes and the activated vascular wall. The medication of mice with simvastatin (2 mg/kg for 2 weeks) reduced the number of the transmigrated CD80 (+) monocytes to peritoneal cavity after intraperitoneal injection of JE/MCP-1. CONCLUSION : Simvastatin directly modulates the functional activity of monocytes, which may prevent arterial wall from the excess accumulation of monocytes/macrophages and subsequent plaque formation.