Interleukin (IL)-33, belonging to the IL-1 family, is a novel cytokine that plays an important role in several chronic inflammatory diseases. Its role in chronic airway inflammation that develops into COPD is widely unknown. To determine this, we identified the expression of IL-33 in human bronchial epithelial layer and detected the inflammatory effects of IL-33 stimulation and the relative signaling pathways in human bronchial epithelial (HBE) cells and peripheral blood mononuclear cells (PBMCs), respectively. In this study, the expression of IL-33 in human bronchial epithelial layer was upregulated in COPD patients compared with normal controls. The expressions of IL-6 and IL-8 were also increased in both HBE cells and PBMCs, stimulated by IL-33 alone or combining the cigarette smoke extract (CSE). And the increased expressions could be partially blocked by ST2-Fc and IL-1RacP-Fc in both HBE cells and PBMCs. The p42/p44 ERK inhibitor in HBE cells and the p38 MAPK inhibitor in PBMCs exerted similar effects. Our data showed that IL-33 could induce and enhance the expression of IL-6 and IL-8 in HBE cells and PBMCs of COPD patients via ST2/IL-1RacP pathway and MAPKs pathway. Thus, the IL-33 is a promoter of chronic airway inflammation that contributes to COPD development.