Under physiological normal conditions, Angiotensin II (Ang II) is involved in the control of arterial blood pressure through its vasoconstrictive effect on vascular smooth muscle cells (VSMC) as well as in the regulation of fluid and electrolyte balance in the kidney. Overeactivity of the renin-angiotensin system has been linked to diseases such as hypertension and atherosclerosis, which are both characterized by abnormal growth of VSMC. As such, Ang II is a growth factor for several cell types, inducing an increase in protein synthesis in VSMC. The octapeptide has also been shown to have pro-inflammatory actions in VSMC inducing the production of cytokines such as MCP-1 and Il-6 and the cell adhesion molecule ICAM-1. The pro-inflammatory action of Ang II is mediated, in part, by the activation of NF-kB family of transcription factors. The molecular basis of the pro-inflammatory actions of Ang II through the activation of NF-kB remains largely unknown. The aim of this study was to verify by which intracellular pathways Ang II activates the NF-kB family of transcription factors. Using in vitro kinase assay, our results show that Ang II induced the activation of the IkB-kinase (IKK) complex in VSMC. The activation of the complex was rapid and transient, with a maximal activation observed after 10 minutes of stimulation. The induction of the IKK complex followed a classical pharmacological profile, being dose-dependent and completely abrogated by the use of the AT1 receptor antagonist, irbezartan. Studies with pharmacological inhibitors revealed that epithelial growth factor receptor (EGFR) transactivation is involved in AT1-mediated activation of the IKK complex. This observation was also confirmed at the molecular level by the use of VSMC overexpressing a truncated version of EGFR. Together, these data suggest that Ang II activates NF-kB transcription factors through the IKK complex. More importantly, the signal by which a heptahelical receptor transduced a pro-inflammatory signal is mediated, at least in part, by the transactivation of the EGFR.