To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy.We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18-70 years. Serum markers of inflammation (high-sensitivity C-reactive protein) and endothelial function (soluble intercell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, endothelin-1 and total nitrite) were assessed using nephelometry, immunoassays and spectroscopy. Diabetic retinopathy was graded from two-field fundus photographs according to the Airlie House Classification system and was categorized into no diabetic retinopathy, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy and vision-threatening diabetic retinopathy, the latter comprising severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or clinically significant macular oedema. Multinomial logistic regression was used to assess the associations between serum markers and diabetic retinopathy.In the study, 64% of patients (144/224) had diabetic retinopathy and 25% (57/244) had vision-threatening diabetic retinopathy. After controlling for age, gender, diabetes duration, HbA1c , systolic blood pressure, total and HDL cholesterol, smoking, the use of insulin or oral hypoglycaemic agents, nephropathy and cardiovascular disease, a positive association was found between increasing high-sensitivity C-reactive protein levels and the presence of vision-threatening diabetic retinopathy (odds ratio 1.26; 95% CI 1.05-1.51, per sd increase in high-sensitivity C-reactive protein). After stratifying by BMI ( ≥ 30 and < 30 kg/m(2) ), this association was found to be more pronounced in people with a BMI ≥ 30 kg/m(2) (odds ratio 2.9; P for interaction = 0.019). No associations were found between serum markers of endothelial activation and diabetic retinopathy.Higher C-reactive protein levels, but not markers of endothelial function, may be related to more severe diabetic retinopathy. This finding suggests that inflammatory processes are involved in severe diabetic retinopathy, particularly in patients with a BMI ≥ 30 kg/m(2) .