It is speculated that more than 400 bacterial species reside in the oral cavity. Some cause inflammation (e.g. periodontitis), understanding of which requires examination of innate immunity in the oral cavity. Oral mucosal cells such as epithelial cells are thought to act as a physical barrier against the invasion of pathogenic organisms, but they have an ability to produce inflammatory cytokines and express adhesion molecules. Oral epithelial cells are refractory to many bacterial components although they express Toll-like receptors/MyD88, and acquire responsiveness after priming with IFN-γ. When the cells are stimulated with lipopolysaccharide (LPS) and neutrophil protease (PR3) after IFN-γ priming, the cells produce bio-active IL-18, which is critical to Th1 and Th2 responses. PR3 itself is able to activate the cells through G protein-coupled protease-activated receptor-2 on the cell surface. These results suggest that innate immune responses of oral epithelial cells to bacterial components are regulated in the inflammatory process. In addition, saliva contains abundant bio-active CD14 from salivary glands in a soluble form, although LPS-binding protein was below detectable levels, suggesting that saliva CD14 is important for the maintenance of oral health.