Objective To investigate the effect and possible mechanisms of progranulin（PGRN） on acute lung injury（ALI） in sepsis. Methods C57BL/6 mice were randomly divided into normal control group（Control group），acute lung injury group（CLP group），and PGRN treatment group（CLP+PGRN group）. Cecal ligation and puncture（CLP） was used to establish a mouse model of septic ALI，and the mice in the CLP+PGRN group were given intraperitoneal injection of PGRN at half an hour after CLP treatment. The mice were anesthetized and sacrificed after 24 hours，and lung tissue was collected for HE staining to observe the pathological damage of lungs； the TUNEL method was used to observe cell apoptosis in lungs；immunofluorescent staining was used to measure the level of nuclear factor-kappa B（NF-κB） in lung tissue；Western blot was used to measure the expression levels of NF-κB，total p65，and phosphorylated p65（p-p65），and RT-qPCR was used to measure the levels of NF-κB and inflammatory factors. Results Compared with the Control group，the CLP group and the CLP+PGRN group had aggravated lung injury and significant increases in proinflammatory cytokines，cell apoptosis in lung tissue，and the expression levels of NF-κB，p65，and p-p65. Compared with the CLP group，the CLP+PGRN group had alleviation of lung injury and apoptosis，a reduction in proinflammatory cytokines，increases in anti-inflammatory cytokines，and significant reductions in the expression levels of NF-κB，p65，and p-p65. Conclusion PGRN can alleviate ALI in mice with sepsis，possibly by inhibiting the expression of NF-κB and p65 and the phosphorylation of p65.