Diabetic retinopathy (DR) is a leading cause of blindness in Western society. Since the prevalence of diabetes continues to increase dramatically, the impact of DR will only worsen unless new therapeutic options are developed. Recent data demonstrate that oxidative stress contributes to the pathology of DR and inhibition of oxidative stress reduces retinal vascular permeability. However, direct mechanisms by which oxidative stress alters the blood-retinal barrier (BRB) and increases vascular permeability remain to be elucidated. A large body of evidence demonstrates a clear role for altered expression of cytokines and growth factors in DR, resulting in increased vascular permeability, and the molecular mechanisms for these processes are beginning to emerge. The pathology of DR is likely a result of metabolic dysregulation contributing to both oxidative stress and cytokine production. This review will examine the evidence for oxidative stress, growth factors, and other cytokines in tight junction regulation and vascular permeability in DR.