Resistin-like molecule (RELM)- is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM- has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM- is strongly induced by diverse allergens and Th2 cytokines by an IL-13 and STAT6 dependent mechanism. To understand the in vivo role of RELM-, we delivered recombinant murine RELM- intratracheally to naive mice. RELM- induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM- was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM- had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM- had fibroblast motogenic activity. These results identify RELM- as a Th2-associated cytokine with potent inflammatory and remodeling activity.