The lung injury score of mice, the lung wet/dry weight ratio, the PaO2/FiO2 ratio, total protein content, total cell and PMNs counts were prominently increased in the CLP group compared with the sham group. 3-MA treatment further aggravated the above indicators. Silencing of GGPPS1 enhanced macrophage autophagy and induced the inactivation of NLRP3 inflammasome to relieve sepsis-induced lung injury. This evidence concerns the gene GGPS1 and Sepsis.