Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) secreted by adipocytes is a member of the CC chemokine family and plays a pivotal role in the inflammatory process. A polymorphism, the -2518 A/G of MCP-1 gene, has been associated with type 2 diabetes, type 1 diabetes, parameters of insulin resistance and obesity. Therefore, we investigated the effects of MCP-1 single nucleotide polymorphisms (SNPs) on the susceptibility to type 2 diabetes or insulin resistance in the Japanese population. We also assessed the correlation between serum MCP-1 concentration and other clinical characteristics in Japanese type 2 diabetic subjects. The serum MCP-1 concentration was significantly correlated with HOMA-IR and the visceral fat area, but not with BMI. Although there was no association between this SNP and type 2 diabetes, the -2518A/G polymorphism was associated with the serum MCP-1 concentration. In subgroup analysis, Japanese obese diabetic -2518AA carriers had a higher MCP-1 concentration and increased insulin resistance than obese diabetic -2518G carriers. These data indicated that the MCP-1 polymorphism was associated with insulin resistance in Japanese obese diabetic subjects and that MCP-1 was implicated in the pathogenesis of insulin resistance, especially associated with obesity, in humans.