Mitochondria are the major source of superoxide (O₂^-) in the aerobic organisms. O₂^- produced by the mitochondria is converted to hydrogen peroxide by mitochondrial superoxide dismutase (SOD2). Mice with complete SOD2 deficiency (SOD2 -/-) exhibit dilated cardiomyopathy and fatty liver leading to neonatal mortality while mice with partial SOD2 deficiency (SOD2 +/-) show evidence of O₂^--induced mitochondrial damage resembling cell senescence. Since earlier studies have provided compelling evidence for the role of oxidative stress and tubulointerstitial inflammation in the pathogenesis of hypertension, we tested the hypothesis that partial SOD2-deficiency may result in hypertension. Wild-type (SOD2 +/+) and partial SOD2-deficient (SOD2 +/-) mice had similar blood pressures at 6-7 months of age but at 2 years, SOD2 +/- mice had higher blood pressure. Oxidative stress, renal interstitial T-cell and macrophage infiltration, tubular damage, and glomerular sclerosis were all significantly increased in 2-year old SOD2 +/- mice. High salt diet induced hypertension in 6-month old SOD2-deficient mice but not in wild type mice. In conclusion, partial SOD2 deficiency results in oxidative stress, renal interstitial inflammation, changes compatible with accelerated renal senescence and salt-sensitive hypertension. These findings are consistent with the pattern described in numerous other models of salt-sensitive hypertension and resemble that commonly seen in elderly humans.