Fischer 344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (Ang) II type 1 (AT₁) receptor blocker L-158,809 on plasma and urinary Ang peptide levels, systolic blood pressure (SBP) and indices of glucose metabolism in 15 month old male F344 rats. Young rats 3 months of age (n = 8) were compared with two separate groups of older rats, one control group (n = 7) and one treated with L-158,809 (n = 6) orally (20 mg/L) for one year. SBP was not different between control and treated rats, but was higher in young rats. Serum leptin, insulin and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma Ang I and Ang II were higher in treated than untreated young or older rats, as evidence of effective AT₁ receptor blockade. Urinary Ang II and Ang-(1-7) were higher in controls compared with young animals and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared to control rats (Young: 8 ± 2 vs Control: 129 ± 51 vs Treated: 9 ± 3 mg/day; p < 0.05). Long-term AT₁ receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) Ang systems occurs during blockade and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury and activation of the intra-renal Ang system during early aging in normotensive animals can be averted by renin-angiotensin system blockade.