Objective: To explore the effect and mechanism of hydroxychloroquine (HCQ) on lipopolysaccharide (LPS) induced neutrophil extracelluar traps (NETs) Methods: Mice were randomly divided into control group, DSS group (3% DSS drinking water+200 μ L pure water by gavage), HCQ+DSS group(3% DSS drinking water+200 μ L HCQ(60mg/kg)by gavage). The disease activity index (DAI) score were evaluated every day. The mice were killed after 7 days, colon length of mice in each group were counted. The pathological changes of colon tissue of mice in each group were observed by HE staining;NETs level was detected by fluorescence microscope and fluorescence microplate reader; Collect the peripheral blood of volunteers to extract neutrophils for experiments in vitro, and detect the level of NETs with fluorescence microscope and fluorescence microplate analyzer;The level of reactive oxygen species (ROS) was detected by fluorescence microplate analyzer after incubation with DCFH-DA fluorescence probe;The protein expression levels of p-MEK, MEK, p-ERK and ERK were detected by Western blot.Results: HCQ alleviates intestinal inflammation in DSS model mice by reduceing the formation of NETs in vivo and in vitro.In vitro, HCQ decreased the release of reactive oxygen species, and inhibited the activation of MEK/ERK signaling pathway. The MEK agonist C16-PAF reversed the inhibition of HCQ on MEK/ERK signaling pathway, enhanced the release of reactive oxygen species, and then increased the formation of NETs.Conclusion: HCQ can reduce DSS induced colitis in mice, and its mechanism may be that it can reduce the release of reactive oxygen species by inhibiting the MEK/ERK signal pathway, thereby reducing the intestinal damage caused by NETs.