This study was designed to evaluate the possible renoprotective effects of rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET-1) production and renal fibrosis associated with inflammation. Rats were implanted with DOCA strips (200 mg kg(-1)) at 1 week after unilateral nephrectomy. DOCA-salt rats received control diet with or without RGT (10 mg kg(-1) per day). Systolic blood pressure was measured by the tail-cuff method. Glomerulosclerosis and tubulointerstitial fibrosis were evaluated on kidney sections. The expression of ED-1, cyclooxygenase-2 (COX-2), heat shock protein-25 (HSP25) and transforming growth factor-beta1 (TGF-beta1) was determined in the kidney by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was increased, whereas creatinine clearance decreased compared with controls, which were counteracted by RGT treatment. Tubular injury and glomerulosclerois in the histological study were prominent in DOCA-salt rats, which were counteracted by RGT treatment. ET-1 expression was increased in DOCA-salts rats, which was attenuated by RGT treatment. The expression of TGF-beta1, ED-1 and COX-2 was increased in DOCA-salt, which was attenuated by RGT treatment. In conclusion, RGT treatment decreases blood pressure and is effective in preventing the progression of renal injury in DOCA-salt hypertension, the mechanisms of which are associated with anti-inflammatory and anti-fibrotic effects through reducing the overexpression of ET-1, ED-1, COX-2 and TGF-beta1 in the kidney.