We investigated that the association of MCP-1 polymorphism at position -2518 with insulin sensitivity and insulin secretion by measuring the fasting and post-challenge glucose and insulin levels during 75g OGTT in 409 non-diabetic Japanese subjects. The blood sampling was performed before glucose loading and after 30 and 120 min. Polymorphism was evaluated by PCR-RFLP method by genomic DNA isolated from peripheral blood leukocytes. The genotype distribution was 44.8% for G/G, 46.0% for G/A and 9.2% for A/A. The plasma glucose levels were significantly increased in A/A as compared to G/G (p<0.05), but it was not compared with G/A at 120 min. The serum insulin levels were significantly increased in A/A as compared to G/A (p<0.05) or G/G (p<0.05) at 30 min. Moreover, the serum insulin levels in A/A were significantly increased compared with G/A (p<0.02) or G/G (p<0.005) at 120 min. Elevation in post-challenge glucose (120 min) and insulin levels (30 and 120 min) suggests that reduced insulin sensitivity during glucose loading occurs in subjects with A/A polymorphism. The present study demonstrates that the A/A polymorphism of the MCP-1 gene at position -2518 is associated with insulin resistance during glucose loading in non-diabetic Japanese subjects.