Abstract: The aim of the present study was to evaluate the protective effect of mangiferin on Human Umbilical Vein Endothelial Cells (HUVEC) against glycated protein-iron chelate induced toxicity. HUVEC incubated in glycated protein either alone or combined with iron chelate showed a significant (p< 0.001) elevation of Lipid Peroxidation (LPO) accompanied by depletion of Superoxide Dismutase (SOD), catalase, Glutathione Peroxidase (GPx) and Glutathione Reductase (GR), in addition to increased microsomal cytochrome c reductase and decreased glutathione S-Transferase (GST). Treatment of HUVEC with mangiferin at a concentration of 5 and 10 μg significantly decreased the level of LPO and altered antioxidants, cytochrome c reductase and GST levels to near normal in a dose dependent manner. Present results suggest that mangiferin have protective effect against glycated protein-iron chelate induced toxicity.