Although the etiology of DME is unclear, an altered local expression of the pleiotropic cytokine tumor necrosis factor (TNF) may play an important role in pathogenesis. Standard treatment of clinically significant DME (i.e. reduction of visual acuity due to DME) consists of laser photocoagulation (two sessions for optimal results?). However, this treatment effectively reduces the risk of vision loss in only 50% of cases. Even among those patients who achieve an initial response recurrences are common, requiring ongoing treatment. Vitreomacular traction or the vitreous itself may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with pars plana vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and improvement in visual acuity. However, this treatment may be applicable only in specific subset of eyes with DME. It also requires a complex surgical intervention with its inherent risks, recovery time and expenses. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors, antibodies targeted at vascular endothelial growth factor (VEGF), intravitreal corticosteroid injection, or high doses of non-steroidal anti-inflammatory agents that lower retinal expression of TNF are under investigation.