The overproduction of reactive oxygen species (ROS) plays a central role in the pathogenesis of endothelial damage in diabetes. To assess the effect of oat on experimental diabetic retinopathy, five groups of Albino rats were studied: nondiabetic control, untreated diabetic, and diabetic rats treated with 5%, 10%, and 20% (W/W) oat of the diet for 12 weeks. Novel data were obtained in this study indicating a protective role of oat against oxidative stress and diabetic retinopathy. The effects of oat on parameters of oxidative stress, AGE, and nuclear factor kappa B (NF-κB) were assessed by ELISA and NF-κB activation by electrophoretic mobility shift assay. Tumor necrosis factor alpha (TNFα) and vascular endothelial growth factor (VEGF) were also determined. After 12 weeks of diabetes, oat treatment reduced blood glucose levels, HbA1c, all oxidative stress markers, CML, normalized NF-κB activation and TNFα expression. Furthermore it reduced VEGF in the diabetic retina by 43% (P < 0.001). In conclusion, oat modulates microvascular damage through normalized pathways downstream of ROS overproduction and reduction of NF-κB and its controlled genes activation, which may provide additional endothelial protection.