The present study evaluated the effects of heme oxygenase-1 induction (HO-1) on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels, during a 45-min renal ischemia and a 30-min. reperfusion in anaesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoforms expression, and renal low molecular weight thiols (SH) were also determined. During ischemia a significant increase in NO levels and peroxynitrite signal were observed (from 832.1±129.3 to 2928.6±502.0 nM and from 3.8±0.7 to 9.0±1.6 nA before and during ischemia, respectively), that dropped to preischemic levels during reperfusion. OMBF and SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure (iARF) was observed (GRF 923.0±66.0 in sham and 253.6±55.3 µL/min/gkwt in ischemized kidneys, p<0.05). The induction of HO-1 (cobalt chloride, 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7±41.0 nM), although eNOS and nNOS expression were slightly increased. CoCl2 administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1315.6±445.6 nM and -6.3±0.5 nA respectively, p<0.05), preserving postischemic OMBF and GFR (686.4±45.2 µL/min/g kidney wt). These beneficial effects of CoCl₂ on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by Sn mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.