Angiotensin II can be associated with gene expression regulation. Thus, We study the possible role of Angiotensin II on the regulation of AT₂ mRNA and protein expression. We utilized sham-operated, renal ablation as well as renal ablation rats pre-treated during the first 7 days of the development of renal damage with either the angiotensin converting inhibitor ramipril, the AT₁ receptor antagonist, losartan, or the AT₂ receptor antagonist, PD123319. Renal tissue was analysed for the histological changes, expression of AT₂ receptor mRNA (by RT-PCR) and protein (by immunohistochemistry). To explore the physiological role of AT₂ receptors over-expression in the development of renal damage, blood pressure urinary protein excretion and renal damage were evaluated. A time-dependent increase in the expression of AT₂ receptor mRNA and protein was observed at 7, 15 and 30 days after renal ablation. Since these effects were already evident at day 7, the effects of ramipril, losartan or PD 123319 were tested at this time. Ramipril as well as PD123319-pretreated group showed inhibition of the AT₂ receptor expression. Whereas the losartan-pretreated group showed further increase in the AT₂ receptor expression . Inhibition of the AT₂ receptor during the renal ablation was associated with increased renal damage and further increase in the blood pressure. Suggesting that over-expression of AT₂ receptors after renal ablation is modulated by Angiotensin II through its own AT₂ receptor and that functional expression of this effect may represents a counter-regulatory mechanism to modulate the renal damage induced by the renal ablation.