Epidemiological studies indicate that acute exposure to particulate matter is associated with significant adverse cardiovascular events. However, the pathophysiological mechanisms responsible for these effects are still unclear.We assessed the direct acute effects of diesel exhaust particles (DEP < 2.5mm) on vasomotor responses. We studied the endothelium-dependent relaxations to acetylcholine (ACh) in rat aortas incubated for 30 minutes with DEP, in presence or in absence of superoxide dismutase (SOD). Endothelium-independent relaxations to sodium nitroprusside (SNP) were also tested (on preparations without endothelium). Aortas were isolated from control rats and rats treated with rosuvastatin (10 mg/kg/d p.o.) for 5 weeks; this treatment down-regulates the p22phox subunit of the NAD(P)H oxidase pathway, considered to be the major source of ROS production in endothelial cells, without alteration in the eNOS pathway. Exposure to 100 mg/ml of DEP caused a decrease in maximal relaxations to ACh from 101.6 ± 2% to 71.8 ± 3.8% (% inhibition of phenylephrine-induced plateau, p < 0.0001). This effect was reversed in presence of SOD (200 UI), indicating that superoxide anion is responsible for the DEP-mediated endothelial dysfunction. Concentration-response curves (CRC) to SNP were slightly but significantly decreased by DEP suggesting a production of superoxide radicals by DEP themselves. In normocholesterolemic rats treated with rosuvastatin, similar results were observed, namely a significant impairment in the Ach-induced relaxations after DEP incubation. This reinforces the hypothesis that DEP themselves produce free radicals. In vivo treatment with apocynin (5 mg/kg/d p.o. for 5 days), an NAD(P)H oxidase inhibitor, also did not protect against this acute toxicity of DEP. The acute vascular toxicity of DEP is resistant to the antioxidant action of statin and apocynin and seems due to a direct generation of superoxide anion by DEP themselves.