Human umbilical vein endothelial cells (HUVECs) were used to investigate the individual effect of ascorbic (0.01 and 0.05 mM) and uric acid (3, 5, and 7 mg/dl), as well as the combined effect of these two agents on glucose-induced overexpression of fibronectin (Fn), glutathione peroxidase (GPx) activity, H2O2 level and vascular endothelial growth factor (VEGF) protein levels. Under 30 mM glucose stress, GPx activity significantly decreased, and lactate dehydrogenase (LDH) release, H2O2 level, and Fn and VEGF production significantly increased in HUVECs (P<.05). The addition of ascorbic acid at 0.05 mM or uric acid at 5 and 7 mg/dl significantly reduced LDH release, recovered GPx activity, suppressed H2O2 production, and decreased Fn and VEGF production (P<.05). The combination of 0.05 mM ascorbic acid and 3, 5, or 7 mg/dl provided significantly greater effect in enhancing GPx activity and lowering H2O2 level than ascorbic acid or uric acid treatment alone did (P<.05). These data suggest that ascorbic acid alone or combined with uric acid in these concentrations may be beneficial to ameliorate glucose-induced diabetic deterioration.