Atrial Natriuretic Peptide (ANP), has protective effect on the outcome of acute renal failure in animals when infused over short periods of time. Escherichia Coli heat-stable enterotoxin (STa) acts on a particulate guanylate cyclase receptors leading to an increase in cytosolic cGMP similar to ANP. STa has longer duration of action and induces significant natriuresis in the healthy kidney, however. Therefore the effects of prolonged infusion of STa and ANP on the outcome of ischemic Acute Renal Failure (ARF) was assessed in the rat. Three groups of rats were used in the experiment, control group (n = 6), had ischemic ARF induced by 30 minutes of left renal pedicle clamping and right nephrectomy. SG group (n = 7) had similar surgery to the control group followed by 1 μg intraperitoneal (i.p) loading dose of STa and placement of mini-osmotic pumps delivering 0.1 μg/hour of STa for 72 hours. AG group (n = 8) also had similar surgery to the control group followed by i.p injection of 10 μg of ANP and placement of mini-osmotic pumps delivering 1 μg/hour of ANP for 72 hours. 72 hours post the induction of ARF, there were no statistical differences among the three groups' creatinine levels, hematocrit and body weights. ANP level was significantly higher in the AG group compared to controls, 5387.6 ± 878.8 and 36.2 ± 10.0 pg/mL respectively, p < 0.001. Urinary sodium (UNa) on the other hand reached highest levels in the SG group compared to controls 16.4 ± 5.0 and 5.0 ± 0.0 meq/L respectively, p = 0.028. In conclusion Sta induces significant natriuresis in ischemic ARF without changing the course of renal impairment. Likewise prolonged infusion of ANP does not alter the course of ischemic ARF.