We tested the hypothesis that elevated levels of plasma high-sensitivity C-reactive protein (HSCRP) are associated with insulin resistance/hyperinsulinemia and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. The study group consisted of 17 type 2 diabetic patients with high HSCRP (0.3-1.0 mg/dL; age, 59+/-8 years, mean+/-SD; high HSCRP group). The control group consisted of 18 age-matched type 2 diabetic patients with low HSCRP (<0.3 mg/dL; 59+/-7 years; low HSCRP group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac metaiodobenzylguanidine (MIBG) labeled with iodine 123 scintigraphic findings. Baroreflex sensitivity was lower in the high HSCRP group than in the low HSCRP group (P<.05). Early and delayed 123I-MIBG myocardial uptake values were lower (P<.05 and P<.005, respectively) and the percent washout rate of 123I-MIBG was higher (P<.01) in the high HSCRP group than in the low HSCRP group. Fasting plasma insulin concentration (P<.01) and the homeostasis model assessment index (P<.01) were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis revealed that the level of HSCRP was independently predicted by fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase. Our results suggest that high levels of HSCRP are associated with depressed cardiovascular autonomic function and hyperinsulinemia and that fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase are independent predictors of HSCRP level in our Japanese patients with type 2 diabetes mellitus.