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) (n¼41, 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 (Po0.0001) and higher homeostasis model assessment (HOMA) index (Po0.00001) 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 (Po0.01 and Po0.05, 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.