Motivation: Hypertension often precedes the diagnosis of type 2 diabetes. It occurs twice as frequently in diabetic patients than in non-diabetic individuals, and aggravates the complications of diabetes. The high susceptibility of individuals with hypertension and diabetes to stroke depends on the sensitivity of the cerebral vasculature to increased blood pressure. It also depends on the occurrence of brain disorders such as capillary rarefaction and astrogliosis of the cerebral cortex caused by associated chronic diseases. Methods: We examined the functional and structural microcirculatory alterations in the brain, skeletal muscle and myocardium of non-diabetic spontaneously hypertensive rats (SHR) and diabetic SHR (D-SHR), as well as the effects of long-term treatment with the angiotensin AT1-receptor antagonist olmesartan (D-SHR OLM) and the angiotensin-converting enzyme inhibitor enalapril (D-SHR ENA). Diabetes was induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, ip). D-SHR were orally administered with olmesartan (5 mg/kg/day), enalapril (10 mg/kg/day) or vehicle for 28 days, and compared with vehicle-treated non-diabetic SHR (SHR VEH) or normotensive non-diabetic Wistar-Kyoto rats (WKY VEH). The cerebral and skeletal muscle functional capillary density of pentobarbital-anesthetized rats was assessed using intravital fluorescence videomicroscopy. All experimental procedures were conducted in accordance with the Care and Use of Laboratory Animals and were approved by the FIOCRUZ Animal Welfare Committee (# LW-10/12). Chronic treatment with OLM or ENA significantly lowered blood pressure and reversed brain functional capillary rarefaction (D-SHR OLM 187 ± 10 or D-SHR ENA 220 ± 38 capillaries/mm2 vs. D-SHR VEH 94 ± 9 capillaries/mm2; p<0.05). Brain oxidative stress was reduced to non-diabetic control levels in animals treated with OLM or ENA. OLM or ENA treatments were able to significantly reduce the number of rolling leukocytes in (D-SHR OLM 5.9 ± 0.1 cells/min; p<0.05 or D-SHR ENA 4.1 ± 0.7 cells/min; p<0.05), when compared with the control D-SHR VEH group (10.6 ± 1.8 cells/min). Histochemical analysis showed that both OLM and ENA increased the capillary-to-fiber ratio in skeletal muscle (D-SHR OLM 2.1 ± 0.1 or D-SHR ENA 2.1 ± 0.1 vs. D-SHR VEH 1.5 ± 0.1; p<0.001) and in the left ventricle (D-SHR OLM 0.23 ± 0.01 or D-SHR ENA 0.30 ± 0.02 Vv[cap]/Vv[fib] ratio vs. D-SHR VEH 0.09 ± 0.01 Vv[cap]/Vv[fib] ratio; p<0.001). OLM or ENA also prevented collagen deposition and the increase in cardiomyocyte diameter in the left ventricle. Our results suggest that the association between hypertension and diabetes results in microvascular alterations in the brain, skeletal muscle and myocardium that can be prevented by chronic blockade of the renin-angiotensin system. Financial support: CNPq