Abstract: Niclosamide (NIC) is one of the commercially molluscicide. With long-term and large-scale using of NIC in China has resulted in ubiquitous environmental and biological safety problems, gradually attracted human attention. Our previous study revealed that acute exposure to NIC disrupted lipid metabolism in zebrafish larvae. Base on that, in our present study, we intended to further study the disruptive effect of NIC on the mechanism in zebrafish embryos/larvae. Healthy zebrafish embryos within 2 h post-fertilization (hpf) were acutely exposed to environmentally realistic concentration of NIC (0, 5, 10, 20 and 40 μg/L, respectively) until 120 hpf. Our results showed that 40 μg/L NIC exposure significantly altered the content of metabolites, such as glucose and lactate, compared with the control. (P < 0.05 and P < 0.05, respectively); additionally, exposure to NIC also significantly inhibited citrate synthase (CS) activity, while a significant increase of lactate dehydrogenase (LDH) activity was observed in 40 μg/L NIC treated group (P < 0.05 and P < 0.05, respectively). Two relative genes, pparα and pparγ, mRNA expressions were significantly increased in 40 μg/L NIC treated group (P < 0.05 and P < 0.05, respectively). Our results indicate that acute exposure to NIC at an environmentally realistic concentration disturbs the metabolism in zebrafish embryos/larvae, as well as alters the expression of genes related to metabolism, changes the activity of enzymes and the contents of metabolites.