We studied whether angiotensin II via superoxide may contribute to retinal leukostasis and thus to the pathogenesis of retinopathies. We studied: 1. whether intravitreal (ivt) angiotensin II induces retinal leukostasis that is altered by antioxidants or by apocynin, a NAD(P)H oxidase inhibitor and 2. Whether retinal leukostasis induced by diabetes in rats is also altered by these treatments. Rats were injected ivt with angiotensin II (20 µg in 2 µl), and divided into three groups: 1. Untreated; 2. Treated with tempol (~70 mg/kg/day) and NAC (~ 1g/kg/day); 3. Treated with apocynin (~ 45 mg/kg/day), both in the drinking water. Rats with streptozotocin-induced diabetes were similarly treated. Leukostasis was evaluated 48 hr after angiotensin II or two weeks after diabetes induction. Angiotensin II increased retinal leukostasis from 0.3 ± 0.5 to 3.7±0.4 leukocytes/ mm² (p< 0.01) and these changes were markedly decreased by treatment with tempol+NAC or apocynin, and also by a blocking antibody against VEGF given ivt (p< 0.01). In addition, incubation of dihydroethidium-loaded retina sections with angiotensin II caused marked increase in superoxide formation. Compared with normal controls, retinal leukostasis in diabetic rats markedly increased from 0.2 ± 0.3 to 3.8 ± 0.1 leukocytes/mm² (p<0.01). Diabetic retinal leukostasis was also decreased by treatment with tempol-NAC and normalized by apocynin. Thus increases in intravitreal angiotensin II can induce retinal leukostasis, that appears mediated via increasing superoxide generation by NAD(P)H oxidase, and by VEGF. The activity of NAD(P)H oxidase is required for leukostasis to occur in the diabetic retina.