Though implicated in vascular remodelling, a role for the resistin-like molecule (RELM)-β in human airway remodelling remains unexplored. We hypothesised that RELM-β expression is increased in the airways of asthmatics and regulates airways epithelial cell function. Expression of RELM-β in the bronchial mucosa and its concentrations in bronchoalveolar lavage (BAL) fluid from asthmatics and controls were measured by immunohistochemistry and ELISA, respectively. Proliferation assays, Western blotting, ELISA and real-time PCR were employed to detect effects of RELM-β on airways epithelial cells. RELM-β expression was increased in the bronchial mucosa and BAL fluid of asthmatics compared with controls. In the asthmatics, the numbers of mucosal RELM-β+ cells correlated inversely with forced expiratory volume in 1 s (r=-0.531, p=0.016), while the numbers of epithelial RELM-β+ cells correlated positively with those of mucin (MUC)5AC+ cells. In vitro, interleukin-13 enhanced RELM-β expression by primary human airways epithelial cells, while RELM-β itself acted on these cells to induce proliferation, expression of MUC5AC, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)-phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation and elevated expression of transforming growth factor-β2, epidermal growth factor and vascular endothelial growth factor. RELM-β has the potential to contribute to airway remodelling in diseases such as asthma by acting on epithelial cells to increase proliferation, mucin and growth factor production, at least partly via ERK/MAPK-PI3K/Akt signalling pathways.