Pigment epithelium-derived factor (PEDF) is encapsulated in poly lactic-co-glycolic acid (PLGA) polymer to prepare PLGA/PEDF emulsions for high efficient inhibitation on vascular endothelial growth factor (VEGF) gene expression. Analyses by Fourier transform infrared spectrum (FT-IR), transmission electron microscopy (TEM) and dynamic light scattering (DLS) proved the formation of the PLGA/PEDF emulsions. Furthermore, CCK-8 assay was used to detect the cytotoxicity of the PLGA/PEDF emulsions to human umbilical vein endothelial cells (HUVEC). Finally, the VEGF levels in the HUVEC cell are tested by enzyme-linked immunosorbent assay at different conditions, such as different concentrations of PLGA/PEDF emulsion, the culture time and the hypoxia treatment. The results showed that the obtained PLGA/PEDF emulsions were good agents for controlled release and inhibit effectively VEGF expression under hypoxia. Therefore, proliferation of HUVEC cells was inhibited by PLGA/PEDF emulsions, and the cell viability of HUVEC cells decreased gradually with increase of concentrations of PLGA/PEDF emulsions.