Abstract: Objective: To investigate the effect and mechanism of quercetin(QUE) on lipopolysaccharide(LPS)-induced inflammatory response in macrophages of mice. Methods: Mouse RAW264.7 macrophages were divided into normal control group, LPS group, and QUE+LPS group. The levels of interleukin(IL)-1β, tumor necrosis factor(TNF)-α and IL-6 in cell culture supernatants were detected by enzyme-linked immunosorbent assay(ELISA). The free zinc content in FluoZin-3 labeled cells was detected by flow cytometry, the levels of ZIP8 mRNA expression in each group of cells were detected by real-time fluorescence quantitative PCR(RT-qPCR), and the expression of ZIP8 protein was detected by western blotting. Results: Compared with the LPS group(1 μg/mL), the contents of IL-1β, TNF-α and IL-6 in the macrophage supernatants of the QUE+LPS group were decreased(P<0.01). Compared with the LPS group, the content of free zinc in macrophages of the QUE+LPS group were decreased(P< 0.05) and the LPS-induced ZIP8 expression were inhibited(P<0.05). Conclusion: QUE can inhibit LPS-induced macrophage inflammatory response, and its effect may be related to down-regulating ZIP8 expression, inhibiting zinc influx, and reducing free zinc content in macrophages.