The present study was conducted to investigate the mechanisms of excessive-fluoride-induced reduction of oocyte development potential in mice. The development morphology of oocyte and the changes of pathomorphology in ovary were observed. The protein expression levels of apoptosis factors, including Bax, Bcl-2, casepase-3, casepase-9 and cytochrome c, and the mRNA expression levels of antioxidant enzymes, including SOD1, GSH-Px1, CAT and inducible nitric oxide synthase were measured by Western blot and real-time PCR, respectively. DNA damage in the ovary was analysed by single cell gel electrophoresis and TUNEL staining. Results indicated that the structure and function of ovarian cells were seriously damaged, followed, the development potential of oocyte was reduced by excessive fluoride. The expression levels of apoptosis factors were up-regulated and antioxidant enzymes were significantly down-regulated. Meanwhile, the contents of ROS, MDA, NO and iNOS were significantly increased. Whereas, the activities of SOD1, GSH-Px1 and CAT was significantly decreased compared with the control group. Simultaneously, the results of DNA analysis indicated that the tail length and tailing ratio of ovarian cells were significantly increased in the fluoride group. In summary, the results provided compelling evidence that excessive fluoride intake can reduce the development potential of oocyte by inducing oxidative stress and apoptosis in the ovary of female mice.