Lycium barbarum polysaccharide (LBP), anactive component from Goji berry which is a traditionalChinese medicine, has anti-inflammatory and antioxidantfeatures. The aim of our study was to investigate whetherLBP has any role in hyperoxia-induced acute lung injury(ALI). Using a murine model of hyperoxia-induced ALI,we investigate the effect of LBP on pulmonary pathologicalchanges as well as Sirtuin 1 (SIRT1) and the nucleotidebinding domain and leucine-rich repeat pyrin domaincontaining 3 (NLRP3) inflammasome. Exposure to 100%oxygen for 72 h in male C57BL/6 mice resulted inincreased protein levels of tumor necrosis factor-a andinterleukin-1b in lung tissues, and aggravated lung histologicalalterations. These hyperoxia-induced changes andmortality were improved by LBP. LBP markedly suppressedthe activation of NLRP3 inflammasome bothin vivo and in vitro. Moreover, LBP upregulated SIRT1expression compared with vehicle-treated group. Importantly,knockdown of SIRT1 reversed the inhibitory effectof LBP on NLRP3 inflammasome activation in vitro. LBP meliorated hyperoxia-induced ALI in mice by SIRT1-dependentinhibition of NLRP3 inflammasome activation.