Objective:To investigate the effect and mechanism of the Lactobacillus reuteri extracts on the macrophages functions in the periodontitis microenvironment.Methods:The optimal concentration of Lactobacillus reuteri extract solution in vitro was explored using RAW264.7.Subsequently,the cells were divided into the PBS control group,the LPS group and the LPS+Lactobacillus reuteri extracts group.The expression levels of multiple inflammatory markers were detected by real-time PCR,ELISA and immunofluorescence staining,and the regulatory mechanism was explored by western blot.In addition,the regulatory effect of Lactobacillus reuteri extracts were investigated in vivo in the rat periodontitis model.Results:50 μg/mL Lactobacillus reuteri extracts solution down-regulated the expression of LPS-induced inos(P<0.05)and Il1b(P<0.01)in RAW264.7 by inhibiting the phosphorylation of p-IκK and p-NF-κB proteins in NF-κB signaling pathway(P<0.01).The expression of TNF-α in RAW264.7 induced by LPS was also inhibited by Lactobacillus reuteri extracts(P<0.05).In vivo results showed that Lactobacillus reuteri extracts reduced the number of osteoclasts(P<0.01)and the TRAP positive area(P<0.05)in periodontitis tissues.Comparing with the bone resorption caused by periodontitis(P<0.01),Lactobacillus reuteri extracts reduced the resorption height of alveolar bone(P<0.05).Conclusion:Lactobacillus reuteri extracts inhibit the LPS-induced inflammatory macrophages activation via NF-κB signaling pathway,and play a protective role in the absorption and destruction of alveolar bone tissue under the inflammatory microenvironment.