OBJECTIVE: To investigate the protective effects of losartan treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques. STUDY DESIGN: Thirty Sprague Dawley female rats were categorized into 3 groups: sham, ischemia-reperfusion (I/R), and I/R+Losartan groups. Ovaries were processed for malondialdehyde (MDA), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and histological tissue protocol. RESULTS: MDA, GSH, and MPO values in control, I/R, and I/R+Losartan groups were compared. Both MDA and MPO values were increased in the I/R group as compared to the control and I/R+Losartan groups. GSH content was increased in the I/R+Lo-sartan group as compared to I/R groups. The control group showed regular ovarian histology. Degenerated follicles, leukocyte infiltration and edema, apoptotic stromal cells, and vascular dilation and congestion were found in the I/R group. There was apoptotic appearance in connective tissue cells in the stromal area. Losartan mostly restored the I/R injury–induced ovarian histology. Fas expression was observed only in some connective tissue cells in the control group; however, it was positive in granulosa cells and stromal cells and endothelial cells in the I/R group. In the I/R+Losartan group, FAS expression was mostly negative. eNOS expression was positive in only some granulosa cells. In the I/R group, intense eNOS expression was observed in theca follicle cells, some granulosa cells, and inflammatory cells. In the I/R+Losartan group, eNOS expression was observed in some connective tissue cells, macrophages, and endothelial cells. CONCLUSION: It is thought that losartan may reduce lipid peroxidation by acting on oxidative stress in the I/R stage and may act to stop the development of degenerative cell apoptosis by affecting the inflammation induced in cell signaling. It has been predicted that the application of losartan may contribute to the development of follicle cells in the ovary and to the preservation of ovarian reserve. © Science Printers and Publishers, Inc.