PURPOSE: Extended warm ischemia during partial nephrectomy can lead to considerable renal injury. Using a rat model of renal ischemia we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury. MATERIALS AND METHODS: A warm renal ischemia model was developed using 60 Sprague-Dawley® rats. The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail of a mixture of specific growth factors, mitochondria protecting biochemicals and Manganese-Porphyrin (MnTnHex-2-PyP(5+)) was given intramuscularly at -24, 0 and 24 hours after surgery. At 48 hours the 2 kidneys were harvested and examined with hematoxylin and eosin, and periodic acid-Schiff stains. Protein and gene expression were also analyzed to determine ischemia markers and the antioxidant response. RESULTS: Compared to ischemic controls, kidneys treated with the renoprotective cocktail showed significant reversal of morphological changes and a significant decrease in the specific ischemic markers lipocalin-2, mucin-1 and galectin-3. Quantitative reverse transcriptase-polymerase chain reaction revealed up-regulation of several antioxidant genes in treated animals. CONCLUSIONS: According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury.