【Objective】 To investigate the role of lipopolysaccharide (LPS) in regulating the inflammatory response of neutrophil through the leucine-rich α-2 glycoprotein 1 (LRG1)/ Rho-associated protein kinase (ROCK1) signaling. 【Methods】 HL-60 cells were treated with 1 μmol/L all-trans retinoic acid (ATRA) and 12.5 μL/mL dimethyl sulfoxide (DMSO) for 72 h and 96 h, and the morphological changes were observed by Wright-Giemsa staining. The expression of CD11b was detected by flow cytometry. LPS induced the activation of dHL-60 and human peripheral blood neutrophils. The transcription and secretion levels of LRG1, ROCK1 and inflammatory cytokines were detected by qPCR and ELISA, respectively. The expression levels of LRG1 and ROCK1 after the activation of dHL-60 were detected by Western blotting. Furthermore, dHL-60 was treated with the recombinant protein LRG1 and ROCK1 inhibitor Y-27632; the transcription levels of inflammatory cytokines were detected by qPCR. 【Results】 Neutrophils were activated by LPS. The expression levels of LRG1 and ROCK1 were significantly increased, and the transcription levels of inflammatory cytokines were significantly increased. The recombinant protein LRG1 activated dHL-60 in vitro, and the transcription levels of ROCK1 and inflammatory cytokines were significantly increased. Using the ROCK1 inhibitor Y-27632, the production levels of inflammatory cytokines were significantly reduced. 【Conclusion】 LPS can regulate the production levels of neutrophil inflammatory cytokines through activating the LRG1/ROCK1 signaling, thus exacerbating the inflammatory response.