Porphyromonas gingivalis is associated with chronic periodontitis, an inflammatory disease of the tooth s supporting tissues. Macrophages are important in chronic inflammatory conditions, infiltrating tissue and becoming polarized to an M1 or M2 phenotype. As responses to stimuli differ between these phenotypes, we investigated the effect of P. gingivalis lipopolysaccharide (LPS) on M1 and M2 macrophages. M1 and M2 polarized macrophages were produced from murine bone marrow macrophages (BMMvarphi) primed with gamma interferon (IFN-gamma) or interleukin-4 (IL-4), respectively, and incubated with a low or high dose of P. gingivalis LPS or control TLR2 and TLR4 ligands. In M1-Mvarphi, the high dose of P. gingivalis LPS (10 mug/ml) significantly increased the expression of CD40, CD86, inducible nitric oxide synthase, and nitric oxide secretion. The low dose of P. gingivalis LPS (10 ng/ml) did not induce costimulatory or antibacterial molecules but did increase the secretion of IL-1alpha, IL-6, IL-12p40, IL-12p70, and tumor necrosis factor alpha (TNF-alpha). P. gingivalis LPS marginally increased the expression of CD206 and YM-1, but it did enhance arginase expression by M2-Mvarphi. Furthermore, the secretion of the chemokines KC, RANTES, eotaxin, and MCP-1 from M1, M2, and nonpolarized Mvarphi was enhanced by P. gingivalis LPS. TLR2/4 knockout macrophages combined with the TLR activation assays indicated that TLR2 is the main activating receptor for P. gingivalis LPS and whole cells. In conclusion, although P. gingivalis LPS weakly activated M1-Mvarphi or M2-Mvarphi compared to control TLR ligands, it induced the secretion of inflammatory cytokines, particularly TNF-alpha from M1-Mvarphi and IL-10 from M2-Mvarphi, as well as chemotactic chemokines from polarized macrophages.