Abstract: This study aimed to elucidate the protective effect and underlying mechanism of epigallocatechin gallate (EGCG) against high glucose-induced pancreatic β-cell developmental anomalies in zebrafish. Zebrafish embryos were exposed to 2 % glucose to induce abnormal pancreatic β-cell development and were pretreated with 10 μmol/L or 50 μmol/L EGCG. Mortality and body length were recorded; and the expression of key genes related to pancreatic β-cell development and function of pancreatic β-cells was detected by RT-PCR. The morphology of pancreatic β-cells in Tg(ins:mCherry) zebrafish was examined under a fluorescent microscope; and glucose levels, as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were measured using commercial kits. The results showed that high-glucose treatment led to an increased mortality rate and body length in zebrafish larvae, along with sustained downregulation in the expression of transcription factors regulating β-cell development. The expression of the insulin a gene (insa) initially increased and then decreased. High-glucose treatment also induced an increase in pancreatic fragmentation and hollow malformations, enlarged islet area, and elevated glucose levels in the body. Furthermore, it caused abnormal activities of SOD, GPx, and CAT enzymes, along with a significant rise in MDA and ROS content in zebrafish larvae. However, intervention with 50 μmol/L EGCG significantly reversed these abnormalities, restored normal β-cell morphology and function, and notably improved the oxidative stress status. In conclusion, EGCG significantly ameliorates high glucose-induced abnormal development of pancreatic β-cells in zebrafish, and its mechanism may be related to the improvement of oxidative stress and glucose levels in zebrafish.