PURPOSE: Subtle changes in retinal vascular caliber have been shown to predict diabetic retinopathy and other diabetic complications. This study was undertaken to investigate whether retinal vascular caliber correlates with light-flicker-induced retinal vasodilation, a measure of endothelial function. METHODS: The participants were 224 persons with diabetes (85 type 1 and 139 type 2) and 103 persons without diabetes (controls). Flicker-induced retinal vasodilation (percentage increase over baseline diameter) was measured with a vessel analyzer. Retinal vascular caliber was measured from digital retinal photographs according to a standardized, validated protocol. Data from both right and left eyes were used and modeled with generalized estimating equations to account for correlation between eyes. RESULTS: In persons with diabetes, after adjustment for age and sex, reduced flicker-induced vasodilation was associated with wider retinal vascular caliber. Eyes with the lowest tertiles of flicker-induced arteriolar dilation had wider arteriolar caliber (5.40 mum; 95% confidence interval [CI], 1.76-9.05) and eyes with the lowest tertiles of flicker-induced venular dilation had corresponding wider venular caliber (12.4 mum; 95% CI, 6.48-18.2), respectively, than eyes with the highest tertile of vasodilation. These associations persisted after further adjusting for diabetes duration, systolic blood pressure, fasting glucose, lipids, body mass index, current smoking, and presence of diabetic retinopathy. No associations were evident in persons without diabetes. CONCLUSIONS: Changes in retinal vascular caliber (wider arterioles and venules) are associated with impaired flicker-induced vasodilation in persons with diabetes. Determining whether endothelial dysfunction explains the link between retinal vascular caliber and risks of diabetic microvascular complications calls for further study.