Recent evidence suggests mineralocorticoid receptor (MR) antagonism has beneficial effects on tissue oxidative stress and insulin metabolic signaling as well as reducing proteinuria. However, the mechanisms by which MR antagonism corrects both renin-angiotensin-aldosterone system (RAAS) impairments in renal insulin metabolic signaling and filtration barrier/podocyte injury remain unknown. To explore this potential beneficial interactive effect of MR antagonism we employed young transgenic (mRen2)27 (Ren2) rats with increased tissue RAAS activity and elevated serum aldosterone levels. Ren2 and aged-matched Sprague-Dawley (SD) controls (age 6-7 wks) were implanted with a low dose of the MR antagonist spironolactone (0.24 mg/day) or vehicle both delivered over 21 days. Albuminuria, podocyte-specific proteins (synaptopodin, nephrin, and podocin), and ultrastructural analysis of the glomerular filtration barrier were measured in relation to RAAS activation of NADPH oxidase and the redox sensitive Rho Kinase (ROK). Insulin metabolic signaling was determined via measurement of IRS-1 phosphorylation, IRS-1 ubiquitin/proteasomal degradation, and phosphorylation of Akt. Ren2 rats exhibited albuminuria, loss of podocyte-specific proteins, and podocyte foot-process effacement contemporaneous with reduced renal IRS-1 and protein kinase B/(Akt) phosphorylation compared to SD controls (each p<0.05). Ren2 kidneys also manifested increased NADPH oxidase/ROS/ROK in conjunction with enhanced renal tissue levels of angiotensin (Ang) II, Ang-(1-12), and Ang type 1 receptor. Low-dose spironolactone treatment reduced albuminuria, tissue RAAS activity, and improved podocyte structural and protein integrity with improvements in IRS-1/Akt phosphorylation. Thus, in this model of RAAS activation MR antagonism attenuates glomerular/podocyte remodeling and albuminuria, in part, through reductions in redox-mediated impairment of insulin metabolic signaling.