Administration of angiotensin II to rats decreases renal expression of klotho, an aging-related gene, and also causes abnormal iron deposition in renal cells. Here we have examined the effects of iron overload and iron chelation on renal expression of klotho in untreated rats and rats treated with angiotensin II. Administration of iron-dextran caused a downregulation of klotho expression, and iron chelation suppressed the angiotensin II-induced downregulation of this gene. In addition, a free radical scavenger (T-0970), which effectively decreased plasma levels of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), suppressed angiotensin II-induced downregulation of klotho. Collectively, these findings suggest that abnormal iron metabolism and increased oxidative stress are involved in the mechanism of angiotensin II-mediated modulation of klotho expression.