Background: Ischemic acute renal failure following renal ischemia/reperfusion injury (IRI) occurs in many clinical situations such as, kidney transplantation 1. One of the mechanisms involved in the development IRI is the development of oxidative stress and decline of antioxidant defense 2. Peroxisome Proliferator Activated Receptor-ɣ (PPAR-ɣ)is ligand-activated nuclear receptor. Recently, a few in vitro studies suggested cross talk between PPARƔ and vitamin D receptor VDR as both are nuclear receptors with involvement of PPAR-ɣ in vitamin D mediated biological responses is a novel mechanism 4 . Aim: the aim of this study was to investigate the effect of acute renal ischemia reperfusion injury, the possible beneficial roles of vitamin D and the mechanism of vitamin D–mediated protection through activation of PPAR-γ on adult male albino rats. Method: The present study was done on 35 adult male albino rats divided into 5 groups : Group I (sham operated group) , Group II: ischemia reperfusion injury group “IRI group") , Group III : "Bisphenol A group " , Group IV: ˝IRI + vit D treated group”, Group V: “IRI + vit D+ Bisphenol A group” . the studied parameters were serum urea , creatinine , tissue level of MDA and SOD and histopathologic study of renal biopsy. Results: renal IRI caused significant increase in serum urea, creatinine and tissue level of MDA and significant reduction in SOD level and was confirmed by histopathologic examination. Vitamin D pretreatment has abolished renal IRI effects. Combined treatment with Bisphenol A and Vit D abolished the vitamin D mediated protection. Conclusion: vitamin D pretreatment had renoprotective effects against renal IRI. The mechanism of that afforded protection mediated by PPAR Ɣ activation.