The most frequently used infection route in Chlamydia pneumoniae animal models is intranasal (i.n.), while the intragastric (i.g.) infection route has not been studied previously. The aim of the present study was to examine the course of Chlamydia pneumoniae infection in mice infected via the i.g. route and to compare the outcome of i.n. reinfection in these mice to i.n. reinfection of primarily i.n. infected mice. C57BL/6JBom mice were used, and the infection was monitored using chlamydial culture, C. pneumoniae PCR and histological examination of several tissues, and antibody measurements. C. pneumoniae was able to disseminate from the gastrointestinal tract to other organs, and i.g. inoculation led to an immunological response. In addition, the primary i.g. challenge made mice more susceptible to i.n. reinfection. In conclusion, the results suggest that the nature of the immune response to a previous C. pneumoniae infection affects the outcome of reinfection.