Background Hydrogen has been reported to exert a therapeutic antioxidant effect via selectively reducing cytotoxic reactive oxygen species(ROS), anti-inflammation and anti-apoptosis in various of diseases.In the present study, we investigated that the link between ovarian damage induced by cisplatin and hydrogen-rich saline treatment.Methods Adult Sprague Dawley virgin female rats weighing 180-220 g were obtained from laboratory animal center of academy of military medical sciences in China.Two hundred and forty animals were randomly divided into four groups (n =60 per group):control(group Con), control with hydrogen-rich saline (group Con+H2), cisplatin-induced ovarian injury(group OI), cisplatin-induced ovarian injury with hydrogen-rich saline (group OI+ H2).Cisplatinwas diluted into saline immediately before use.In group OI and group OI+ H2, the rats received a single dose of cisplatin.The rats were intraperitonealy injected by hydrogen-rich saline at 10ml/kg body weight once a day during 2 weeks(14 days) the same as cisplatin injection weekly.Atl4th, 28th, and 42th day(T1, T2 and T3) after thecisplatin and hydrogen-rich saline injection, femoral vein blood was collected from the rats(n=10) and centrifuged at 10, 000g , 4℃ for 10 min.After the experiment, ovarian homogenates were prepared and centrifuged by the same method.These sample werestoredat-80℃ until the analysis of estrogen(E2),follicle stimulating hormone(FSH), superoxide dismutase(SOD), catalase(CAT) and malondialdehyde(MDA) examination.After experiment, rats (n=10) were killed to remove the bilateral ovary, one of which was fixed in formalin for follicle counting analysis, while the other was used for nuclear factor erythroid 2-related factor 2(Nrf2) detection by Western blot.Results Hydrogen-rich saline attenuated the FSH release and elevated the level of E2at T1, T2 and T3 time in ovarian injury rats.Hydrogen-rich saline(H2) could improved the development of follicles and the damage of the cortex.Cisplatin led to oxidative stress via increasing the levels of oxidative products and attenuate the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment.Hydrogen-rich saline may regulate the Nrf2 / antioxidant response elements(ARE) protein expression in in ovary insult rats.Conclusions: Hydrogen-rich saline had protective effect on cisplatin-induced ovarian injury via reducing MDA and increasing SOD and CAT activity.Also, high Nrf2 expression was involving with ovarian injury.