Aims/hypothesis: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. Methods: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45° fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. Results: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. Conclusions/interpretation: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy. © Springer-Verlag 2005.