Objective: To determine the relation of glycemia, blood pressure, and serum total cholesterol level as systemic markers of inflammation and endothelial dysfunction to the prevalence and incidence of diabetic retinal outcomes in persons with long-duration type 1 diabetes mellitus. Methods: Longitudinal population-based study of persons with type 1 diabetes mellitus who received care for their diabetes in south central Wisconsin from July 1, 1979, to June 30, 1980. Data for this investigation were obtained from the 1990-1992 through the 2005-2007 follow-up examinations. Main outcome measures included the severity of diabetic retinopathy (DR) and macular edema (ME). Results: In the 1990-1992 prevalence data, soluble vascular cell adhesion molecule, tumor necrosis factor, and homocysteine levels were associated with increased odds of more severe DR (odds ratios [highest vs lowest quartile], 3.95 [95% confidence interval, 1.66-9.39], 5.46 [2.38-12.52], and 7.46 [2.91-19.16], respectively) in those with kidney disease while controlling for relevant confounders. Similar odds were found for proliferative DR. Only total homocysteine level was associated with increased odds of ME(3.80 [95% confidence interval, 1.91-7.54]), irrespective of kidney disease. None of the markers were associated with incidence of proliferative DR, ME, or progression of DR 15 years later. Conclusions: A limited number of markers are associated with increased odds of prevalent retinal outcomes in persons with type 1 diabetes mellitus and kidney disease. Only homocysteine level is associated with ME in those with and without kidney disease. In the absence of kidney disease, the markers do not add to the more conventional descriptors and predictors of DR in persons with type 1 diabetes mellitus. This may reflect the close association of DR and kidney disease in diabetic persons.