Abstract: Objective To explore the correlation between Toll like receptor (TLR) 4 on monocyte in peripheral venous blood and chronic periodontitis (CP). Methods Peripheral venous blood samples were obtained from 15 CP patients and 10 healthy control (HC) subjects that were recruited from the Second Affiliated Hospital of Liaoning Medical University from February to March in 2015, then flow cytometry was used todetect the expression of monocyte TLR4 and IL-6, and enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of IL-6 in plasma. After culturing, THP-1 cells were given the following stimulations: 0.9% normal saline (NS), lipopolysaccharide (LPS), anti-TLR4 and anti-TLR4 + LPS respectively for 6 h, then the expression changes of TLR4 and IL-6 in NS, LPS and anti-TLR4 were compared to confirm the result of peripheral venous blood experiment and the expression changes of TLR4 and IL-6 in anti-TLR4 and anti-TLR4 + LPS were compared to investigate whether the TLR4 induced signal pathway could be a novel therapeutic target of CP. Results Compared with HC group, the expressions of monocyte TLR4 and IL-6 and the IL-6 level in plasma were significantly higher in CP group (P< 0.001). Expressions of TLR4 in protein and mRNA and the level of IL-6 in THP-1 in LPS group were significantly higher than NS group (P=0.019, P< 0.001, P< 0.001). After blocking TLR4, compared with LPS group, expressions of TLR4 in protein and mRNA and the level of IL-6 in THP-1decreased significantly (P< 0.001). There were no significantdifferences in TLR4 expression and IL-6 level between anti-TLR4 group and anti-TLR4 + LPS group. Conclusion LPS from G- can cause the increase of TLR4 expression on monocyte and monocytes stimulated by TLR4 can upregulate the level of pro-inflammatory cytokines, which play a role in chronic periodontitis pathogenesis. Signaling pathway ofTLR4 recognizing LPS may be a novel therapy target for chronic periodontitis.