Purpose: To investigate whether vitreous levels of vascular endothelial growth factor (VEGF) and pigment epitheliumderived factor (PEDF) are related to diabetic macular edema (DME). Design: Retrospective case-control study. Participants: Thirty-six patients with DME,6 diabetic patients without retinopathy,and 13 patients with nondiabetic ocular disease. Methods: After vitreous fluid samples were obtained at vitreoretinal surgery,VEGF and PEDF levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. Main Outcome Measures: Correlations between vascular permeability and the vitreous fluid levels of VEGF and PEDF. Results: The vitreous level of VEGF was significantly higher in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P < 0.0001 and P < 0.0001,respectively). Convers-ely,the vitreous level of PEDF was significantly lower in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P < 0.0001 and P < 0.0001,respectively). The vitreous level of PEDF did not correlate significantly with that of VEGF (P=0.1806). The vitreous level of VEGF was significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P=0.0022). Conversely,the vitreous PEDF level was significantly lower in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P=0.0172). Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P < 0.0001 and P=0.0469,respectively). Conclusions: Our retrospective study suggests that VEGF and PEDF have an independent association with vascular permeability in the eye and on the DME,and we recommend that prospective validation of our findings be undertaken to confirm these observations. Purpose: To investigate whether vitreous levels of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) are related to diabetic macular edema (DME). Design: Retrospective case-control study. diabetic patients without retinopathy, and 13 patients with nondiabetic ocular disease. Methods: After vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. Main Outcome Measures: Correlations between vascular permeability and the vitreous fluid levels of VEGF and PEDF. Results: The vitreous level of VEGF was significantly higher in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P <0.0001 and P <0.0001, respectively). Convers-ely, the vitreous level of PEDF was significantly lower in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P <0.0 001 and P <0.0001, respectively) The vitreous level of PEDF did not correlate significantly with that of VEGF (P = 0.1806). The vitreous level of VEGF was significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0022) .Conversely, the vitreous PEDF level was significantly lower in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P < 0.0001 and P = 0.0469, respectively). Conclusions: Our retrospective study suggests that VEGF and PEDF have an independent association with vascular permeability in the eye and on the DME, and we recommend that prospective validation of our findings be undertaken to confirm these observations.