Porphyromonas gingivalis, a periodontopathic bacterium, is known to invade oral epithelial cells in periodontal lesions, although the mechanism is unclear. In the present study, goat polyclonal anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody inhibited the invasion of P. gingivalis into KB cells (human oral epithelial cells). Further, the P. gingivalis fimbria, a pathogenic adhesion molecule, bound to recombinant human ICAM-1, as shown by enzyme-linked immunosorbent assay. P. gingivalis was also found to colocalize with ICAM-1 on KB cells, as seen with an immunofluorescence microscope, and the knockdown of ICAM-1 in KB cells resulted in the inhibition of P. gingivalis invasion by RNA interference. In addition, methyl-beta-cyclodextrin, a cholesterol-binding agent, inhibited the colocalization of P. gingivalis with ICAM-1 and invasion by the microorganism. The colocalization of caveolin-1, a caveolar marker protein, on KB cells with P. gingivalis was also shown, and the knockdown of caveolin-1 in KB cells caused a reduced level of P. gingivalis invasion. These results suggest that ICAM-1 and caveolae are required for the invasion of P. gingivalis into human oral epithelial cells, and these molecules appear to be associated with the primary stages of the development and progression of chronic periodontitis.