Purpose: Diabetic retinopathy (DR) is a chronic microvascular diabetic complication leading to visual loss. Ranibizumab (RBZ) is a monoclonal antibody inhibiting VEGF-A, approved for DR treatment. 4-Methyl catechol (4MC) is a potent NGF stimulant & possesses a neuroprotective effect in neuronal diseases. The aim of this study was to evaluate the role of 4MC in comparison to RBZ in the progression of streptozotocin (STZ) induced-diabetic retinopathy in albino rats. Methods: This experiment was performed on 40 albino rats divided equally into: (normal control, untreated DR, RBZ treated intravitreally & 4MC treated intravitreally). Results: The untreated DR group revealed a significant elevation of fasting serum glucose, VEGF-A, histopathological score & IHC score of Tie-2, and a significant decrease in NGF, and IHC of Bcl-2 versus the normal control group. Treatment with either RBZ or 4MC produced significant improvement in the forementioned parameters when compared to the untreated DR group. Conclusion: RBZ and 4MC are effective in the progression of STZ-induced DR via inhibition of VEGF-A and stimulation of NGF respectively.