The objective of the present study was to evaluate the efficacy of nateglinide in controlling blood glucose levels and regulating lipid metabolism in patients with type 2 diabetes by focusing attention particularly on low-density lipoprotein (LDL) particle size. The subjects were 23 patients with type 2 diabetes who were given nateglinide, 90 to 270 mg/d. Laboratory studies were conducted at treatment initiation and 3 mo later. Despite a decline that occurred in the level of fasting plasma glucose before and after administration of nateglinide, no significant difference was recognized. Hemoglobin A1c decreased significantly from 6.37+/- 0.75% to 5.91+/-0.64% (P<.001). A significant decline was also seen in the fasting level of immunoreactive insulin, from 9.82+/-5.69 microU/mL to 8.59+/-4.05 microU/mL (P<.05), and in the homeostasis model assessment for insulin resistance, from 3.06+/-1.83 to 2.55+/-1.26 (P<.05). Regarding lipids, triglycerides significantly decreased from 140.7+/-61.8 mg/dL to 117.3+/-34.7 mg/dL )P<.05). The significant reduction in migration index value, which was used as an index to LDL particle size, from 0.374+/-0.034 to 0.357+/-0.035 (P<.05), confirmed that LDL particle size had increased. The results of the present study show that nateglinide is effective in controlling blood glucose and improving insulin resistance, hypertriglyceridemia, and LDL particle size in patients with mild type 2 diabetes. These effects suggest that nateglinide may effectively control coronary artery disease in this population.