Angiotensin II (AngII) is a cytokine that participates in renal damage. Vascular endothelial growth factor (VEGF) is constitutively expressed in the kidney and is involved in the progression of renal disease. The aim of this work was to investigate the relation between AngII and VEGF and the mechanisms involved in its regulation in the kidney. We have observed that in cultured tubuloepithelial cells (NRK52E cell line) AngII increased VEGF gene expression and promoter activation. Hypoxia-inducible factor-1 (HIF-1) is one of the main VEGF gene activators. AngII induces HIF-1alpha protein production and increases HIF-1 DNA-binding activity. An antisense HIF-1alpha oligodeoxynucleotide inhibited AngII-induced VEGF overexpression. The reactive oxygen species act as second messengers in kidney damage caused by AngII and mediate the induction of HIF-1 by cytokines. In tubuloepithelial cells, VEGF up-regulation and HIF-1alpha induction due to AngII were significantly diminished by antioxidants, suggesting a redox-mediated mechanism. Infusion of AngII into mice caused renal VEGF overexpression, HIF-1 activation, and oxidative stress. In summary, these data show that AngII in vivo and in vitro up-regulates renal VEGF expression by a mechanism that involves HIF-1 activation and oxidative stress.