To assess effects of fluoride (F) and lead (Pb) on the energy metabolism of the male reproductive system, the activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), and Gamma-glutamyltranspeptidase (?-GT), along with sperm quality and testicular histology, were determined at week 6, 8, 10, and 12 in male offspring rat pups exposed in their drinking water either to sodium fluoride (150 mg/L=HiF) or to lead acetate (300 mg/L=HiPb). Compared with the control, LDH activities were significantly increased, whereas SDH activities were decreased in the HiF and HiPb group. Both F and Pb resulted in lower ATPase activity. Additionally, changes in ?-GT activities were also observed, which were decreased in the HiF group and increased in the HiPb group. In contrast to the control group, the F-treated and Pb-treated rats exhibited a marked decline in sperm density and sperm viability along with a significant increase of sperm abnormalities over the entire 12-week study period. Moreover, F and Pb obviously affected the testicular histology, finally resulting in significant increases in the diameter and thickness of seminiferous tubules. Therefore, F and Pb may share a similar reproductive toxic mechanism by which disordered energy metabolism in the testis and epididymis influenced the sperm quality.