Fusobacterium nucleatum is an important endodontic pathogen, and prostaglandin E2 (PGE2) has important roles in the development and progression of inflammatory responses. In this study, we investigated the effects of F. nucleatum on PGE2 production in human dental pulp cells (HDPCs). Cells were stimulated with F. nucleatum and PGE2 protein and cyclooxygenase (COX)-1/2 mRNA levels determined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. The activation of mitogen-activated protein (MAP) kinases was examined by Western blotting. F. nucleatum strains increased PGE2 production by HDPCs in a dose-dependent manner. Moreover, strain 10953 made a stronger response than strain 49256. F. nucleatum dosedependently increased COX-2 mRNA levels without affecting COX-1 expression. Furthermore, celecoxib, a selective COX-2 inhibitor, blocked PGE2 production by F. nucleatum. Finally, F. nucleatum activated all three MAP kinases. The pharmacological inhibition of each MAP kinase significantly attenuated F. nucleatum-induced PGE2 production. These results suggested F. nucleatum induced COX- 2-mediated PGE2 production by HDPCs by activating MAP kinases, thereby promoting endodontic inflammation.