Cyclooxygenase-2 (COX-2)-mediated prostaglandin E2 (PGE2) plays important roles in the development and progression of inflammatory responses and Porphyromonas gingivalis is a common endodontic pathogen. In this study, we investigated the induction of COX-2 and PGE2 by P. gingivalis in human dental pulp cells (HDPCs). P. gingivalis increased expression of COX-2, but not that of COX-1. Increased levels of PGE2 were released from P. gingivalis-infected HDPCs and this PGE2 increase was blocked by celecoxib, a selective COX-2 inhibitor. Furthermore, P. gingivalis activated all three types of mitogen-activated protein kinases (MAPKs). P. gingivalis-induced activation of nuclear factor-κB (NF-κB) was also demonstrated by the results of phosphorylation of NF-κB p65 and degradation of inhibitor of κB-α (IκB-α). Pharmacological inhibition of each of three types of MAPKs and NF-κB substantially attenuated P. gingivalis-induced PGE2 production. These results suggest that P. gingivalis should promote endodontic inflammation by stimulating dental pulp cells to produce PGE2.