Diabetic retinopathy (DR) is a complex pathophysiological event and a major cause of blindness in diabetic patients. The pathways that have been proposed to explain the pathogenesis of DR include many events; all starting from hyperglycemia. Among the most important pathways are: increased oxidative stress, inflammation, activation of ocular RAS and retinal neuronal cell death. Based on this background, the present study was designed to evaluate and compare the possible retinoprotective effects of insulin to other studied drugs either alone or in combination including: atorvastatin as an antihyperlipedemic, losartan as an ARB, EGb761 as an antioxidant on the following parameters: HBA1c %, serum MDA concentration, retinal histopathological changes and retinal VEGF and ICAM-1 after induction of DR by STZ in rats. The most significant retinoprotective effect recorded among the drug treated groups was for the insulin group followed by the other treated goups in the following order: losartan plus atorvastatin group, losartan plus EGb761 group, losartan group, atorvastatin group and finally EGb761 group.