Diabetic retinopathy (DR) and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. Seventy persons were diagnosed to have type 2 diabetes in the examination from June 2004 to May 2006. The study group consisted of 29 type 2 diabetic patients with DR (age: 58+/-6 years, mean+/-s.d.) and 41 type 2 diabetic patients with no DR (NDR) (n=41, 58+/-5 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. DR patients had lower BRS, early and delayed (123)I-MIBG myocardial uptake values and higher percent washout rate (WR) of (123)I-MIBG than the NDR patients. With respect to metabolic findings, DR patients had higher fasting plasma insulin concentration (P<0.0001) and higher homeostasis model assessment (HOMA) index (P<0.00001) than the NDR patients. Multiple logistic regression analysis revealed that the presence of DR was independently predicted by HOMA index and the percent WR of (123)I-MIBG (P<0.01 and P<0.05, respectively). Our results suggest that DR is associated with depressed cardiovascular autonomic function and insulin resistance and that HOMA index and the percent WR of (123)I-MIBG are independently associated with DR in Japanese patients with type 2 diabetes mellitus.