Rationale: Cysteinyl leukotrienes and the Th-2 cytokines IL-5 and IL-13 directly modulate human airway smooth muscle functions such as contraction and proliferation. Objectives: We studied the effects of other lipid mediators involved in asthma pathophysiology such as PGD₂, lipoxin, and isoprostanes, and the cytokines, IL-5, IL-4 and IL-13 on human airway smooth muscle cell migration. Methods: Chemotaxis and chemokinesis of cultured non-asthmatic human airway smooth muscle cells (2^nd-5^th passages, n=6) were studied using collagen-I coated polycarbonate membranes in Transwell culture plates. Receptor expression and kinase activation were studied by flow cytometry, polymerase chain reaction and western blotting techniques. Results: In contrast to LTE₄- stimulated (10^-6M) chemokinesis and LTE₄-primed migration towards PDGF, isoprostane 15-F_2t-IsoP, and IL-5 were neither chemotactic nor chemokinetic. PGD₂ (10^-10-10^-6M) was a chemoattractant and primed migration towards PDGF through the DP₂/CRTh₂ receptor. Although airway smooth muscle cells did not express the lipoxin A₄ cognate receptor, LTE₄-primed migration towards PDGF was blocked by lipoxin A₄(10^-6M), suggesting that this is mediated through CysLT₁R antagonism. IL-13 (10 ng/ml), but not IL-4 (0.1-100 ng/ml), augmented migration towards PDGF. This was associated with increased Src-kinase phosphorylation and upregulation of PDGF- and -receptors, and attenuated by IL-13R and IL-4R neutralizing antibodies, a Src-kinase antagonist (PP1, 3 µM), a CysLT₁R antagonist, montelukast (10^-6M), and by lipoxin A₄ (10^-6M). Conclusion: PGD₂ and IL-13 promote human airway smooth muscle migration. IL-13 can promote airway smooth muscle migration through Src-kinase and leukotriene-dependant pathways. This may contribute to the accumulation of smooth muscle cells in remodelled airway submucosa.