Macular edema following diabetic retinopathy is one of the ocular complications associated with diabetes, and it is the leading cause of visual loss in the active young and middle aged population in developed countries. While all patients with diabetes particularly those with diabetic retinopathy are at increased risk of developing eye complications, early detection and timely intervention may prevent or delay loss of visual acuity. Systemic management of diabetes through combined control of blood sugar, hypertension, and hyperlipidemia has remained the most effective method to prevent diabetic retinopathy and its progression. Development of diabetic retinopathy and related complications require, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection to preserve vision. Considering recently most popular treatment of diabetic macular edema(DME) including intravitreal anti-vascular endothelial growth factor(VEGF) agents, several issues such as ideal regimen, duration of treatment, combination therapy and long-term safety have remained unanswered yet and deserve further investigations. In this review, all the articles that had investigated such treatment modalities for DME as well as pharmacokinetic, efficacy, safety, dose and frequency of intravitreal pharmacologic agents and also the effect of macular ischemia, initial macular thickness and optical coherence tomographic patterns of DME on the final outcomes of treatment with Intravitreal drugs are reviewed. In summary, literature searches reveal that almost all studies that have been published up to now provide some evidence that support the use of intravitreal anti-VEGF agents for treatment of either nve or persistent DME in short and long term up to two years. Macular edema following diabetic retinopathy is one of the ocular complications associated with diabetes, and it is the leading cause of visual loss in the active young and middleaged population in developed countries. While all patients with diabetes particularly those with diabetic retinopathy are at increased risk of developing eye complications, early detection and timely intervention may prevent or delay loss of visual acuity. System of management of diabetes through combined control of blood sugar, hypertension, and hyperlipidemia has remained the most effective method to prevent diabetic retinopathy and its progression. diabetic retinopathy and related complications require, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection to preserve vision. issues s uch as ideal regimen, duration of treatment, combination therapy and long-term safety have remained unanswered yet and deserve further investigations. In this review, all the articles that had conditioned such treatment modalities for DME as well as pharmacokinetic, efficacy, safety, dose and frequency of intravitreal pharmacologic agents and also the effect of macular ischemia, initial macular thickness and optical coherence tomographic patterns of DME on the final outcomes of treatment with Intravitreal drugs are reviewed. In summary, literature searches reveal that almost all studies that have been published up to now provide some evidence that supports the use of intravitreal anti-VEGF agents for treatment of either nve or persistent DME in short and long term up to two years.