Retinal vessels may provide a way to study the cerebral microcirculation. In particular, larger retinal venular diameters have been associated with cerebrovascular disease. An inflammatory response may underlie this association. In a population-based cohort study among 5,279 participants aged 55 years or older with graded retinal vessel diameters, we observed that greater serum levels of C-reactive protein and fibrinogen and greater lipoprotein-associated phospholipase A(2) activity were strongly associated with larger venular diameters. Weaker associations were found with arteriolar diameters. Our findings support the hypothesis that larger retinal venular diameters reflect systemic inflammation and suggest that inflammation is involved in cerebrovascular disease.