Diabetic retinopathy is a great ocular diabetic disorder and may cause blindness. It is linked with hyperglycemia, inflammation and oxidative stress. Adiponectin is an adipokine that has antioxidant, anti-inflammatory and anti-angiogenic effects. Objective: to detect possible role of adiponectin as a therapy in experimentally induced diabetic retinopathy in male adult rats. Material and Methods: Thirty male adult rats were divided into 2 groups: group Ι (control 10 rats) and group II (diabetic type 1 induced by streptozotocin, 20 rats). Diabetic rats were divided four weeks later into 2 subgroups: Subgroup IIA (diabetic retinopathy), Subgroup IIB (adiponectin-treated diabetic retinopathy), in all groups, serum glucose, insulin, lipid profile, superoxide dismutase (SOD), malonaldehyde (MDA), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) and aquaporin-4 (AQP4) gene expression were estimated. Retinal histopathology and immunohistochemistry of retinal VEGF and tumor necrosis factor (TNF) alpha were also estimated. Results: Subgroup IIB showed significant decrease in serum levels of glucose, cholesterol, triglyceride, low density lipoprotein (LDL), MDA, VEGF and IL-6, and AQP4 gene expression, with significant increase in insulin, SOD and high-density lipoprotein (HDL) levels. Retinal histopathology showed partial restoration of retinal layers organization and immunohistochemistry showed downregulation of TNF-α and VEGF. Conclusion: Adiponectin may improve diabetic retinopathy via antioxidant, anti-inflammatory, antidiabetic and anti-angiogenic effect.