Chalcones, prepared in high yield in polyethylene glycol, Mw = 300 (PEG300), were screened for inhibition of the thrombin-mediated release of pro-inflammatory interleukin-6 (IL-6) and interleukin-8 (IL-8) from the A549 lung epithelial cell line. Several show significant down-regulation of these pro-inflammatory mediators in a dose-dependant manner with one exhibiting pro-inflammatory properties. Computational studies on selected chalcones revealed a detailed understanding of the structure, electron density and biological activity relationship. © 2009 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.