The pathogenesis of septic acute renal failure (ARF) involves systemic vasodilation with compensatory upregulation of vasoconstrictors. This can lead to renal vasoconstriction and ARF. Heme Oxygenase is the rate limiting step in heme metabolism and produces carbon monoxide (CO) and biliverdin. HO-1 is an inducible form of the enzyme and is expressed in response to cell injury. It was hypothesized in endotoxemia, induction of HO-1 would lead to increased production of the vasodilator CO, lower blood pressure, and decrease renal function. The role of HO-1 was therefore examined in a mouse model of endotoxemia. One group of mice received LPS alone and were compared to mice that received LPS in addition to an inhibitor of HO-1, zinc protoporphyrin (ZnPP). Treatment of mice with LPS resulted in significant increases in the protein expression of HO-1 as compared to controls treated with vehicle. Immunohistochemical analysis localized this upregulation to both the proximal and distal tubules as well as the vasculature. Hemodynamic studies were performed during endotoxemia and the mean arterial pressure (MAP) was found to be significantly higher in the HO-1 inhibitor treated as compared to vehicle treated mice (78 ± 3 mmHg versus 64 ± 2 mmHg, p<0.01). It was found that the inhibitor group had higher renal blood flows (RBF) also during endotoxemia (1.8 ± 0.2 ml/min versus 0.68 ± 0.1 ml/min, p<0.01). Furthermore, when renal vascular resistance (RVR) was calculated there was a significant decrease in RVR in the inhibitor group (43.5 ± 3.4 mmHg/ml/min vs. 95.9 ± 11.3 mmHg/ml/min, p<0.01). In concert with the hemodynamic data, glomerular filtration rate (GFR), as measured by inulin clearance, was higher in the HO inhibitor as compared to the vehicle controls during endotoxemia (111.5 ± 19.5 µl/min versus 66. ± 3.5 µL/min, p<0.05). In summary, during endotoxemia ARF, inhibiting HO- 1 with ZnPP resulted in the protection of renal function. The renal protection was associated with significantly improved systemic hemodynamics, less renal vasoconstriction, and a higher GFR.