Airborne particulate pollutants, such as DEPs are thought to exacerbate lung and cardiovascular diseases through induction of oxidative stress. Sulforaphane, derived from cruciferous vegetables, is the most potent known inducer of phase II enzymes involved in the detoxification of xenobiotics. We postulated that sulforaphane may be able to ameliorate the adverse effects of pollutants by up-regulating expression of endogenous antioxidant enzymes. Stimulation of bronchial epithelial cells with the chemical constituents of diesel particles result in the production of pro-inflammatory cytokines. We first demonstrated a role for phase II enzymes in regulating diesel effects by transfecting the airway epithelial cell line (BEAS-2B) with the sentinel phase II enzyme NQO1. IL-8 production in response to diesel extract was significantly reduced in these compared to untransfected cells. We then examined whether sulforaphane would stimulate phase II induction and whether this would thereby ablate the effect of diesel extracts on cytokine production. We verified that sulforaphane significantly augmented expression of the phase II enzyme genes GSTM1 and NQO1 and confirmed that sulforaphane treatment increased GST activity in epithelial cells without inducing cell death or apoptosis. Sulforaphane pre-treatment inhibited IL-8 production by BEAS-2B cells upon stimulation with diesel extract. Likewise, whereas diesel extract stimulated production of IL-8, GM-CSF, and IL-1 from primary human bronchial epithelial cells, sulforaphane pre-treatment inhibited diesel-induced production of all these cytokines. Our studies show that sulforaphane can mitigate the effect of diesel in respiratory epithelial cells and demonstrate the chemopreventative potential of phase II enzyme enhancement.