AIM: To investigate how vascular endothelium growth factor (VEGF) contributes to the expression of pigment epithelium-derived factor (PEDF) in retina of rats and evaluate the neuroprotection of VEGF for retinal ganglion cells (RGCs) of rats with chronic intraocular hypertesion and it''s potential approach. METHODS: Thirty female adult Sprague Dawley rats were randomly divided into three groups: elevated intraocular pressure (EIOP) + VEGF ( group A, including A3d, A14d),EIOP +placebo (group B, including B3d, B14d), normal + VEGF (group C, including C3d, C14d). The model of EIOP were established by obstructing episcleral veins in group A and B, only open the bulber conjunctiva without obstructing episcleral veins in group C. In group A and C, shortly after episcleral veins were cauterized, rats were intravitreously injected 2μL VEGF (concentration: 0.05μg/μL) at 2.0mm behind the limbus of cornea. To keep the IOP, 2μL vitreous body were drawn out before the intravitreous injection. In group B, 2μL H₂O were intravitreously injected. Three days and 14 days later, the animals were sacrificed and the eye balls were cut with cryostat, then TUNEL staining protocol were carried out to detect apoptotic cells and degenerate neurons in the retina. Immunofluorescent double labeling was performed to identify which cells were PEDF-positive cells in the retina.RESULTS:The IOP was obviously increased after the operation(P＜0.05), there was no significant difference in IOP between 3 days and 14 days after the operation. TUNEL-positive cells and FJ-positive cells in retina of chronic intraocular hypertension group were much more than that of normal group. The number of TUNEL-positive cells in retinas of chronic intraocular hypertension+ VEGF group was reducing. CONCLUSION: Intravitreal administration of VEGF has the effect of reducing the apoptosis of the RGCs in rats with chronic intraocular hypertension. 