A total of 84 healthy female mice were kept with various concentrations of sodium fluoride (F) (0, 50, 100, 150 mg F–/L in drinking water for 90 days) and were then mated with healthy male mice for 1 week to study the effect of excessive fluoride on female reproductive function, particularly in embryo implantation. The rate of pregnancy, litter size, and the birth weight of female mice were evaluated. Ultrastructural changes of uteri tissues were observed by transmission electron microscopy (TEM). The mRNA expression levels of MMP-9 and TIMP-1 were determined by quantitative real-time PCR. The protein expression levels of MMP-9 and TIMP-1 were analyzed by western blotting. Results showed a significant decrease of litter size in mice exposed to fluoride. TEM images of uteri tissue of mice that underwent a 150 mg/L F– treatment for 90 days showed a vague nucleus, reduced microvilli, increased lysosomes, a dilated endoplasmic reticulum, and a vacuolization mitochondrion when compared with the control group. Following the damage of the structure, the expression levels of MMP-9 and TIMP-1 in uteri tissues were significantly unregulated in the F 150 group. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions.