Abstract: Objective: To explore the differences in inflammatory responses between oral polymorphonuclear neutrophil (oPMN) and circulating polymorphonuclear neutrophil (cPMN), and the roles of oPMN in maintaining periodontal health. Methods：cPMN was obtained from peripheral venous blood of healthy individuals by density gradient centrifugation, while oPMN was collected from oral rinses of healthy subjects by centrifugal filtration. Both of PMNs were stimulated with 1μg/ml Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS was employed as a positive control. Apoptosis levels and phagocytosis of P. gingivalis or E. coli by two PMNs were assessed by flow cytometry. Moreover, after IL-8 stimulation, chemotactic responses of the cells were determined by a transwell migration assay. Production of interleukin (IL)-1β, IL-8 and IL-10 were analyzed by ELISA. Formation of neutrophil extracellular traps (NETs) was observed by immunofluorescence staining and levels of extracellular DNA were quantified by Sytox Green fluorescence staining. Furthermore, phosphorylation of mitogen?activated protein kinase1/2 (MEK1/2), extracellular regulated protein kinases1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) were measured by Western blot. Results：After P. gingivalis/E. coli LPS stimulation, higher levels of apoptosis in oPMN were disclosed compared with cPMN (p<0.05). No significant difference was confirmed in chemotactic ability of the two PMNs after IL-8 stimulation (p>0.05). Expression levels of IL-1β, IL-8 and IL-10 in oPMN were higher compared with cPMN (p<0.05) and more quantities of P. gingivalis or E. coli were phagocytized by oPMN than cPMN (p<0.05). Moreover, more quantities of NETs, higher levels of extracellular DNA, and greater phosphorylation levels of MEK1/2, ERK1/2 and NF-κB P65 were revealed in oPMN compared with cPMN (p<0.05). Conclusion：oPMN might be an overactive phenotype of neutrophil with increased capacities of phagocytosis, NET formation and cytokine secretion compared to cPMN, which might be associated with the increased phosphorylation of MEK1/2, ERK1/2 and NF-κB.