To investigate the expression of vascular endothelial growth factor (VEGF)and the levels of reactive oxygen species (ROS)in human mesangial cells cultured in high glucose and being intervened by pigment epithelium-derived factor (PEDF). The results showed that with increased glucose concentration, the expressions of VEGF and ROS generation also gradually increased and PEDF significantly downregulated VEGF expression and ROS generation in a dose-dependent manner. PEDF may delay the diabetic nephropathy progress by improving vascular permeability and inhibiting oxidative stress.