Hydroxysafflor yellow A (HSYA) is an active ingredient obtained from the flower of Carthamus tinctorius L. The present study investigated the effects of HSYA on lipopolysaccharide (LPS)-induced inflammatory signal transduction in human alveolar epithelial A549 cells. A549 cells stimulated with LPS were incubated with three doses of HSYA (1,4 and 16 mu mol/L). HSYA suppressed the expression of TLR-4, Myd88, ICAM-1, TNF alpha, IL-1 beta and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells. HSYA treatment also decreased NF-kappa B p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). These findings suggest that HSYA effectively inhibits LPS-induced inflammatory signal transduction in A549 cells. Crown Copyright (c) 2012 Published by Elsevier B.V. All rights reserved.