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Renal ischemia reperfusion injury promotes tissue damage through inducing uncontrolled inflammation, oxidative stress and excessive renal tubular epithelial cell death. Nrf2 pathway is essential in protecting the kidney against renal IRI. Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor, Canagliflozin attenuated nephrotoxicity possibly through its anti-inflammatory and antioxidant effects and may confer renoprotective effects independently of its glycemic effects. To study the Nephroprotective potential effect of Canagliflozin renal ischemia reperfusion injury in rats model via modulation of Nrf2 pathway. In this study, adult male rats of Westar Albino type with 18-28 weeks in age and weighing 300-350 g were randomized into equal four groups (6 rats each group) as following: Sham group, Control group, Vehicle (DMSO) group, Canagliflozin treated group. Rats were subject to bilateral renal ischemia for 30 min by clamping and reperfusion for 2 hr. We conclude that Canagliflozin significantly decrease renal ischemia reperfusion injury in rat model through Nrf2 pathway via it is pleiotropic effects as anti-oxidant, anti-inflammatory and anti-apoptotic. [ABSTRACT FROM AUTHOR]