Chlamydia, especially Chlamydia pneumoniae, infection is closely associated with human cardiovascular diseases. Thus far, however, few experimental studies have been carried out to investigate whether natural C. trachomatis infection can induce cardiovascular pathological changes. In this article, we report that pulmonary infection with C. trachomatis mouse pneumonitis strain (MoPn) can induce myocardial and perivascular inflammation and fibrosis in C57BL/6 mice. The pulmonary MoPn infection appeared to be disseminated systemically, because chlamydial antigens were readily detectable in multiple organs including the cardiovascular tissues. In addition, gamma interferon gene knockout mice with a C57BL/6 genetic background showed significant endocarditis and pancarditis characterized by vegetation in aortic valves, interstitial and pericardial inflammatory cellular infiltration, and growth of the organisms in the heart following respiratory tract MoPn infection. The results indicate that C. trachomatis can induce cardiovascular diseases following respiratory tract infection and suggest that murine MoPn respiratory tract infection may be a useful experimental model for investigating cardiovascular diseases caused by chlamydial infection.