Objective To investigate into the signaling pathway of Porphyromonas gingivalis(P.gingivalis) on cytokine expression in human dental pulp cells(HDPC). Methods Anaerobic method was employed to culture P. gingivalis, and then HDPC were intracellularly infected by P.gingivalis. The extraction of total RNA, real -time quantitative polymerase chain reaction(qPCR) and enzyme linked immunosorbent assay(ELISA) was used for mRNA expression of Nods and Rip2, protein secretion of interleukin-6(IL-6). Results HDPC expressed Nods, Rip2 mRNA and IL-6. The up-regulation of Nods and Rip2 mRNA started after P.gingivalis infection, reached maximal level at 2 h, and then decreased at 6 h; whereas elevated IL-6 was found when P.gingivalis infected. Conclusion P.gingivalis activate host innate immune responses in HDPC, and induce IL-6 production through Nod/Rip2-mediated signaling pathway.