Niclosamide (NIC) is the most widely used molluscicides for preventing the occurrence of schistosomiasis disease, and its residues can be found in various environmental samples. However, the toxicity mechanism of NIC during early developmental stage remains largely unknown. In the present study, zebrafish embryos were acutely exposed to NIC at an environmentally realistic concentration (0 and 40 mu g/L) until 120 h post-fertilization. Transcriptomic sequencing was performed to provide mechanistic insight into developmental impairment. Pathway enrichment analyses found that biological processes related to lipid metabolism were significantly affected in exposed zebrafish larvae. Consistently, biochemical measurements showed that NIC developmental exposure depleted lipid storage, elevated lipid utilization, but inhibited lipid synthesis. Furthermore, as characterized by pathway enrichment and hormonal levels, steroid hormone biosynthesis was also significantly disrupted by NIC exposure in zebrafish larvae, indicating the endocrine disrupting potential of NIC. Detoxifying phase I and II processes (e.g., metabolism, conjugation and elimination) were significantly activated by NIC exposure. Overall, our findings suggest that NIC developmental exposure at an environmentally realistic concentration disturbs the lipid metabolism, induces endocrine disruption and initiates detoxifying capacity in zebrafish larvae, which will provide preliminary clues for developmental toxicity mechanisms of NIC. (C) 2019 Elsevier Ltd. All rights reserved.