Renal ischemia/reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 hours post-reperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R; and that acute low dose testosterone is protective by: 1) increasing renal IL-10 and reducing TNF-α; 2) it's effects on nitric oxide (NO); and 3) reducing intrarenal T cell infiltration. Rats were subjected to renal I/R followed by intravenous infusion of vehicle or testosterone (20, 50 or 100 μg/kg) 3 hrs post-reperfusion. Low dose testosterone (20 μg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10 and reduced intrarenal TNF-a, whereas 50 μg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-α; a higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-α compared to other groups. Low dose nitro-L-arginine methyl ester (1 mg/kg/d), given 2 days prior to I/R, prevented low dose testosterone (20 μg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4+ and CD8+ T cells were significantly increased with I/R but were attenuated with low dose testosterone as were effector T helper 17 cells. The present studies suggest that acute, low dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than pro-inflammatory cytokines.