Recent studies have shown that diesel exhaust particles (DEP) have adverse effects on the respiratory tract in vitro and in vivo, related to various pro-inflammatory cytokines and inflammatory mediators. The inflammation induced by the production of cyclooxygenase (COX)-2, an important mediator of inflammation and tumor promotion, and excess eicosanoids may be central to the pathogenesis of DEP-induced airway inflammation. However, the role of COX-2 in the pathogenesis of DEP-induced lung inflammation remains unclear, especially in vivo. In this study, we demonstrated that treatment with 50 microg/ml of DEP for 24h induced the expression of the COX-2 gene at both the transcriptional and protein levels, which led to an increase in the release of prostaglandin E(2) (PGE(2)) in A549 cells. In addition, the increased levels of COX-2 and PGE(2) by DEP exposure were significantly suppressed by treatment with 50 pg/ml of dexamethasone (Dex). We also showed that exposure to 25 mg/kg of DEP induced the expression of the COX-2 protein in mouse lung tissues, and this increased COX-2 expression was attenuated by pretreatment with 5 mg/kg of Dex. These findings suggest that COX-2 may play an important role in the pathogenesis of DEP-induced pulmonary inflammation, which is effectively inhibited by glucocorticoid treatment.