Objective:To study the effects of endotoxin tolerance induced by subgingival plaques on the productions of inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 and the protein expressions of Toll-like receptor 2, 4 (TLR2, 4)in human macrophages. Methods:Macrophages were pretreated with subgingival plaques from moderate to serve chronic periodontitis patients or healthy controls (24h), washed (2h)and treated with the same plaques again (24 h). Levels of TNF-α and IL-10 in supernatant were detected by ELISA. Moreover, TLR2, 4 protein expressions in these cells were explored by flow cytometry. Results:The amounts of TNF-α and IL-10 secreted by macrophages stimulated with both kinds of subgingival plaques were increased significantly after 24h(P < 0.05). After repeated stimulation with the same plaques, secretions of TNF-α were decreased significantly compared with those following single challenge(P < 0.05), while only comparable levels of IL-10 were confirmed in both two kinds of plaques- tolerized cells(P > 0.05). However, no significant changes of TLR2 and 4 were detected in macrophages retreated with these plaques compared with those following single stimulations. Conclusion:Secretions of TNF-α could be suppressed by endotoxin tolerance induced by subgingival plaques, which might contribute to limiting periodontal inflammation. However, development of this tolerance might not be affected by TLR2 and 4.