AIM: To determine the aqueous, vitreous, serum levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR), and to speculate on the source of the change in concentration and to discuss its clinical significance. METHODS: Forty-one eyes with proliferative diabetic retinopathy were included in the study, 16 of which were complicated by neovascularization of iris (NVI). Twenty-one eyes with idiopathic macular hole (MH) were as controls. The aqueous, vitreous, serum levels of PEDF and VEGF of all the groups were determined with ELISA. PEDF, VEGF and the levels in the three groups were compared with analysis of variance (ANOVA). The PEDF, VEGF concentrations in aqueous, vitreous and serum were analyzed with Pearson correlation test, and the correlation of PEDF and VEGF levels was also analyzed with Pearson correlation test. RESULTS: The aqueous levels of PEDF decreased significantly in sequence in groups of control, PDR without NVI, PDR with NVI. VEGF levels increased coordinately. The similar findings existed in vitreous samples. The PEDF, VEGF levels in aqueous were not correlated significantly with those in serum, but correlated positively with those in vitreous. The intraocular levels of PEDF had a negative correlation to those of VEGF. CONCLUSION: The reduction of intraocular PEDF level and elevation of intraocular VEGF level may play an important role in the occurrence and progression of PDR. In the development of PDR, the PEDF,VEGF levels in aqueous may be mainly effected by local pathological changes, as anti-angiogenic and pro-angiogenic factors, their unbalanced intraocular distribution may promote the angiogenesis of the iris and retina.