In this study, a metabolomic analysis was used to reveal the neurotoxicity of the CdTe/ZnS QDs via microglia polarization. A gas chromatography-mass spectrometer (GC-MS) was applied to uncover the metabonomic changes in microglia (BV-2?cell line) after exposure to 1.25?μM CdTe/ZnS QDs. 11 annotated metabolic pathways (KEGG database) were significantly changed in all exposed groups (3?h, 6?h, 12?h), 3 of them were related to glucose metabolism. The results of the Seahorse XFe96 Analyzer indicated that the CdTe/ZnS QDs increased the glycolysis level of microglia by 86% and inhibited the aerobic respiration level by 54% in a non-hypoxic environment. In?vivo study, 3?h after the injection of CdTe/ZnS QDs (2.5?mM) through the tail vein in mice, the concentration of the CdTe/ZnS QDs in hippocampus reached the peak (1.25?μM). The polarization level of microglia (Iba-1 immunofluorescence) increased 2.7 times. In?vitro study, the levels of the extracellular TNF-α, IL-1β and NO of BV-2?cells were all increased significantly after a 6?h or 12?h exposure. According to the results of the Cell Counting Kit-8, after a 6?h or 12?h exposure to the CdTe/ZnS QDs, the exposed microglia could significantly decrease the number of neurons (HT-22?cell line). This study proved that CdTe/ZnS QDs could polarize microglia in the brain and cause secondary inflammatory damage to neurons. There are potential risks in the application of the CdTe/ZnS QDs in brain tissue imaging.,Copyright ? 2019 Elsevier Ltd. All rights reserved.