Cystic fibrosis (CF) is characterised by chronic airway inflammation. Pro-inflammatory mediators in the lung are regulated by the transcription factor nuclear factor kappa B (NFκB). We have assessed the effect of adenovirus and liposome-mediated overexpression of the NFκB inhibitor IκBα, as well as liposome-mediated transfection with oligonucleotides resembling NFκB consensus binding sites (decoys) in a cystic fibrosis airway epithelial cell line (CFTE). Electrophoretic mobility shift assays (EMSA) were used to assess NFκB activity and secretion of the pro-inflammatory cytokine interleukin-8 (IL-8) was measured by ELISA. At a MOI of 30, Ad-IκBα significantly decreased IL-8 secretion to 60% and 43% of control unstimulated and TNF-α stimulated cells, respectively. At this MOI, approximately 70% of cells are transduced. EMSA showed an approximately 50% decrease in NFκB activation. Liposome-mediated transfection of IκBα did not reduce IL-8 secretion, probably due to low transfection efficiency (approximately 5% of cells). Liposome-mediated transfection of CFTE cells with rhodamine-labeled decoy oligonucleotides indicated a transfection efficiency close to 100%. TNF-α stimulated IL-8 secretion was reduced by approximately 40% using this approach. EMSA confirmed a significant decrease of NFκB activation. Decoy oligonucleotides may be a promising approach for reduction of NFκB-mediated pulmonary inflammation.