Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis(P. gingivalis). Porphyromonas gingivalispeptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalisstrain in which the PPAD gene was deleted (Δppad) and a Δppadstrain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad,or comΔppadtwice a week for the entire 40 days (days 0−40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31−40). P. gingivalisand comΔppadexacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppadfailed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppadincreased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppadwith T lymphocytes in vitro and found that P. gingivalisand comΔppadsignificantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalisexacerbated the severity of UC in part via PPAD.