Polybrominated diphenyl ethers (PBDEs) are now found ubiquitously in the aquatic environment and biota, and there is a growing concern that PBDEs may disrupt endocrine systems, leading to reproductive impairments of aquatic animals. In our study, zebrafish (Danio rerio) were exposed to the 5 ng/L, 1 μg/L and 50 μg/L of DE-71 for the duration of the whole life cycle (120 days, from eggs to adults). The expression of selected genes along the brain-pituitary-gonadal (BPG) axis and liver, and the levels of plasma sex hormones were examined. In male fish, up-regulation of GnRH in brain, FSHβ and LHβ in pituitary, FSH-receptor, LH-receptor, and CYP19a in testis was clearly evident, while down-regulation of CYP11a and 3β-HSD was found in testis. In female fish, a 2.4-fold up-regulation of 3β-HSD was found in ovary upon exposure to 50 μg/L of DE-71. GnRH in brain, FSHβ and LHβ in pituitary were also up-regulated, while ERβ, TH and TPH in brain and GnRH-receptor in pituitary were significantly down-regulated. Hepatic ERα, AR and VTG in males were all down-regulated, while hepatic ERα and AR in female were up-regulated. Serum estradiol (E2) was reduced in both male and female upon exposure to DE-71, while significant increases in serum testosterone (T) and 11-keto-testosterone (11-KT) were only found in male but not female fish. The ratio of T/E2 as well as the ratio of 11-KT/E2 in male fish increased in a dose-dependent manner upon exposure to DE-71. Our overall results showed that whole life exposure of DE-71 altered the expression of regulatory genes and receptors at all three levels of the BPG axis in zebrafish, and the responses are sex dependent. The observed disruption of GnRH and GtHs can be further related to the subsequent disruption in both levels and balance sex steroid hormones.