Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There is currently no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly utilised the murine model; however, infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals, with MOMP-specific IgG and IgA present in the vaginal mucosae, and high levels of MOMP-specific IgG detected in the serum. Antibodies from the vaginal mucosae were also capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with 10(2) inclusion forming units of live C. caviae. We observed a decrease in the duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP-immunised animals, compared with animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract pathology in r-MOMP-immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, by reducing not only chlamydial burden, but also upper reproductive tract pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.