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Objective(s): Ischemia/reperfusion (I/R) is the leading cause of acute kidney injury. This study aimed to elucidate the reno-protective effect of gamma-oryzanol (GO) by comparing gavage and intraperitoneal (IP) administration methods on renal I/R injury in a rat model. Materials and Methods: Rats were divided into four groups including (group 1) sham, (group 2) I/R-control, (group 3) I/R+GO gavage-treated, and (group 4) I/R+ GO IP-treated. A single dose of GO was administrated to groups 3 and 4 (100 mg/kg body weight), 60 min before induction of I/R. After anesthesia, I/R was created by 45 min of ischemia, followed by 6 hr of reperfusion. Then, blood and tissue samples were subjected to evaluation of renal function, anti-oxidant capacity, inflammation, apoptotic proteins, and IKB/NF-kB pathway.Results: The two GO administration methods showed improvement of renal function along with attenuation of histological abnormalities. An increase in antioxidant capacity along with a decrease in pro-inflammatory markers, decline in the expression levels of BAX, Bax/Bcl-2, and caspase-3, and up-regulation of Bcl-2 expression were recorded. Moreover, a significant decrease in NF-Kb, p-IKBα, and MMP-2/9 with an increase in IKBα levels were also observed. Overall, in a comparative evaluation between the two gavage and IP administration methods, we did not find any differences in all examined parameters, except IL-6 which had a better result via gavage.Conclusion: A single dose of GO administration has a reno-protective effect against renal I/R injury. Gavage and IP administration exhibit similar efficiency in alleviation of I/R injury.