Pigment epithelium‐derived factor (PEDF) down‐regulates vascular endothelial growth factor (VEGF) of retinoblastoma both in vitro and in vivo. SO‐Rb50 cells were incubated with or without PEDF (100 nmol/L) for 10 h under normoxia and hypoxia. Immunocytochemistry and western blotting assays were explored to analyze the effect of PEDF on VEGF. (a) Immunocytochemistry analysis of VEGF expression in SO‐Rb50 cells (×640). (b,c) Western blotting analysis for VEGF in tumor cells and tumor tissues, respectively. H, hypoxia; H + P, hypoxia + PEDF (100 nmol/L); N, normoxia; N + P, normoxia + PEDF (100 nmol/L). Values significantly lower than control (**P < 0.01, ##P < 0.01, *vs normoxia control, # vs hypoxia control, *P < 0.05, #P < 0.05) are indicated.