Background: Chlamydia pneumoniae infection has been strongly associated with atherosclerosis. However, the mechanisms responsible for the atherogenic effects of C pneumoniae are yet to be elucidated. PPAR�� activation exerts anti-atherogenic effects through direct effects on the vascular wall, especially inhibiting proliferation and migration of vascular smooth muscle cells (SMC). This study investigated whether C pneumoniae infection could suppress the expression of PPAR�� in vascular SMC. Methods: Rabbit aortic smooth muscle cells (RSMC) and human coronary artery smooth muscle cells (CASMC) were infected with C pneumoniae. PPAR�� mRNA and protein expression were assessed after different periods of infection (0, 6, 24, and 48 h postinfection) by real time RT-PCR and Western blot analysis. It was also examined whether treatment with rosiglitazone could attenuate the suppression of PPAR�� mRNA and protein in infected SMC. Results: Cell numbers were maintained at 48 hours after infection. Expression of PPAR�� mRNA and protein was significantly reduced as early as 6 hours postinfection compared to uninfected controls and further reduced as time elapsed in RSMC (P<0.0001) and CASMC (P<0.0001). Treatment of C pneumoniae-infected CASMC with rosiglitazone significantly attenuate the suppression of PPAR�� mRNA expression. Conclusion: C pneumoniae infection leads to the suppression of PPAR�� expression in vascular SMC. These data suggest that suppression of PPAR�� may be an important event responsible for the atherogenic effects induced by C pneumoniae.