[Objective] To validate the immune protective efficacy of Chlamydia secretion protein Pgp3 and to analyze the potential immune mechanisms related to this protection. [Methods] The prokaryotic recombinant protein Pgp3 was purified and evaluated for its pro-tective efficacy in a genital tract infected mouse model. Groups of BALB/c mice were immu-nized intranasally or intramuscularly with adjuvants plus Pgp3 protein or PBS and GST con-trol. Humoral and cellular immune responses were evaluated. After Chlamydia muridarum in-travaginal challenge, the chlamydia shedding from the lower genital tract and the chlamy-dia-induced upper genital tract gross pathology and histopathological characterization were also detected. [Results] Adjuvant plus Pgp3 immunization can induce high level of Pgp3 spe-cific antibody as well as IFN-γ, IL-17 and IL-5 cytokine production. More importantly, intra-nasal immunization compare with intramuscular route induced more Th1-dominant immunity that significantly reduced the shedding of live organisms from the lower genital tract and at-tenuated inflammatory pathologies in the oviduct tissues. [Conculsion] These observations have demonstrated that secretion protein Pgp3 intranasal immunization can induce protective immunity against chlamydial infection and pathology in mice.