Inflammation is pivotal to the pathogenesis of diabetic retinopathy (DR). Hypertension is the main secondary risk factor associated with DR. The mechanisms by which hypertension increases the risk for DR are poorly understood. The aim of the current study was to investigate the contribution of genetic hypertension to early retinal inflammation in experimental diabetes. Diabetes was induced in 4-week-old (developing hypertension) and 12-week-old (fully hypertensive) spontaneously hypertensive rats (SHR) and age-matched control normotensive Wistar Kyoto (WKY) rats by administration of streptozotocin (50 mg/kg, i.v); after 20 days the rats were sacrificed and the retinas were collected. ED1 positive cells, ICAM-1 and VEGF levels were significantly higher in diabetic SHR in both prehypertensive and hypertensive ages (p < 0.005). NF-kappaB p65 levels were higher in prehypertensive SHR and in hypertensive diabetic SHR (p < 0.05). Induction of diabetes in normotensive WKY rats did not show any alteration in retinal expression of inflammatory parameters. Therefore, we conclude that the developing hypertension and also the fully developed hypertension lead to earlier development of inflammation in diabetic retina. Aggravation of the inflammatory process may be involved in the mechanism by which essential hypertension exacerbates retinopathy in the presence of diabetes.32533-41