Backgrounds:Ischemia-reperfusion (IR) injuries occur in a variety of clinical conditions, which lead to kidney damage. Most of the tissue damages after IR are due to the activation of the renin–angiotensin system (RAS). Hence, in this study, the interaction of sex hormones and RAS in ovariectomized (OV) rats subjected to IR induction has been studied.Materials and Methods:The animals were divided into different groups. Groups 1 (OV + E, OV rat + estradiol) and 2 (OV rat) each one consisted of three separate IR-induced subgroups treated with losartan, angiotensin 1–7 (Ang 1–7), and their combination, Group 3, as control and Group 4, as sham. Next, 72 h after IR, blood samples were collected, the right kidneys were homogenized, and left kidneys were fixed in 10% formalin.Results:Findings show that serum blood urea nitrogen, creatinine, and kidney tissue damage score levels increased significantly with induction of IR (P < 0.05). Mean serum levels of these factors in OV + E groups are higher than those of the OV. The presence or absence of estradiol did not affect the levels of antioxidants in the different groups receiving Los, Ang 1–7, and their combination. Los, Ang 1–7, and their combination reduced serum and kidney malondialdehyde levels in both OV and OV + E groups.Conclusion:Estrogen not only fails to improve renal functioning but it can also exacerbate it. While the treatments used in this study, in the absence of estradiol, it had a better effect on kidney damages and improved its functions.