Long-term administration of angiotensin II causes myocardial loss and cardiac fibrosis. We previously found that iron deposition occurred in the heart of angiotensin II-infused rat, which may act to promote angiotensin II-induced cardiac damage. In the present study, we have investigated whether an iron chelator (deferoxamine) and a free radical scavenger (T-0970) affect the angiotensin II-induced upregulation of transforming growth factor-1 (TGF-1). Angiotensin II infusion for seven days caused a robust increase in the TGF-1 mRNA expression in the vascular smooth muscle cells, myofibroblast-like cells, and migrated monocytes/macrophages. Both T-0970 and deferoxamine suppressed the upregulation of TGF-1 mRNA and reduced the extent of cardiac fibrosis in the heart of rats treated with angiotensin II. These agents blocked the angiotensin II-induced upregulation of heme oxygenase-1, a potent oxidative and cellular stress-responsive gene, but did not significantly affect the systolic blood pressure or plasma levels of aldosterone. In addition, both T-0970 and deferoxamine suppressed the angiotensin II-induced upregulation of monocyte chemoattractant protein-1 (MCP-1) in the heart. These results collectively suggest that iron and the iron-mediated generation of reactive oxygen species may contribute to angiotensin II-induced upregulation of profibrotic and proinflammatory genes, such as TGF-1 and MCP-1.