The association between ambient particulate matter (PM) and cardiovascular diseases has been demonstrated in epidemiological studies. Recent studies suggest that diabetic patients are at greater risk for PM-associated cardiovascular events. Although diabetes and PM exposure individually have been reported to be associated with increased oxidative stress, inflammation, and endothelial dysfunction, it is not clear whether PM may induce synergistic interaction effects on these parameters in diabetics. Strepotozotocin-induced diabetic (n=4) and healthy (n=4) rats were intratracheally administered with PM2.5 collected from a busy traffic area in a dose of 200 microg suspended in 0.5 mL phosphate-buffered saline (PBS). The same number of rats was exposed to PBS as controls. Cell and differential counts and protein and lactate dehydrogenase activity were determined in bronchoalveolar lavage. Markers of 8-hydroxydeoxy-guanosine (8-OHdG), endothelin-1 (ET-1), and [nitrate+nitrite], an indicator of nitric oxide (NO) production, in addition to C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood were also determined. Our results showed that diabetic rats were associated with increased 8-OHdG, IL-6, and ET-1 decreased [nitrate+nitrite]. In nondiabetic rats PM exposure was also associated with increased 8-OHdG, IL-6, TNF-alpha, and CRP but decreased [nitrate+nitrite]. Interestingly, increases of 8-OHdG and ET-1 after PM exposure were more prominent in diabetic rats than in nondiabetic rats. The general linear model further indicated that there were interactions between diabetes and PM on 8-OHdG (P<0.01) and ET-1 (P=0.08). We suggest that PM exposure may enhance the risk of cardiovascular diseases through interaction between PM and diabetes on excess reactive oxygen species generation and endothelial dysfunction. These findings provide further support for previous epidemiological studies.