Background: Acute kidney injury (AKI) is a common worldwide disorder that is associated with high morbidity and mortality. Its pathophysiology is complex including a triad of oxidative tissue damage, inflammation and activation of clotting cascade. Objective: Investigating the outcome of vitamin E acetate administration immediately after the induction of renal ischemia/reperfusion injury on its progression. Materials and Methods:  The present study was carried out on 48 adult female Wister rats, weighing 185-250 grams, randomly allocated into the following 3 groups: Sham-operated group (SHAM; n^ₒ=18), renal ischemia/reperfusion injury group (RIR; n^ₒ=20), and renal ischemia/reperfusion injury group treated with Vitamin E Acetate (RIR_ttt; n^ₒ=10).  Rats were subjected to measurement of initial and final body weights (IBW, FBW), absolute and relative kidney weights (AKW, RKW), serum level of urea and creatinine as renal function tests, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrin degradation products (FDPs) as markers of blood coagulation, C-reactive protein (CRP) as an inflammatory marker, as well as plasma and renal tissue malondiadehyde (MDA_p, MDA_t) as oxidative stress markers, in addition to histopathological study of the kidney tissue. * The majority of preclinical studies in AKI were performed in males (Skrypnyk et al., 2016), so we focused to study the effect of RIR in female rats independent of estrus cycle. Results: RIR rat group showed significant increase in AKW, RKW, as well as serum levels of urea and creatinine compared to sham operated group, but there was no significant change in their PT, APTT, FDPs, CRP, MDA_p, and MDA_t compared to the sham operated group. RIR_ttt rat group exhibited insignificant changes in their AKW, RKW, serum urea, creatinine, PT, APTT, FDPs, CRP, MDA_p, and MDA_t compared to RIR. Histopathological study of RIR rat kidneys showed glomerular congestion with periglomerular edema and atrophy of some glomeruli as well as cystic tubular dilation with esinophilic cast with tubular epithelial necrobiosis, and these changes were not improved by vitamin E treatment in RIR_ttt rat kidneys. Conclusion: Vitamin E acetate administration in a single dose of 1000 mg/kg B.W. immediately after induction of RIR could not interfere with the progression of AKI as proved by the non significant changes in kidney function tests and histopathological picture.