Glucocorticoids (GCs) exert a therapeutic effect in numerous chronic inflammatory diseases. However, chronic obstructive pulmonary disease (COPD) tends to be GC-resistant. Icariin, a major component of flavonoids isolated from Epimedium brevicornum Maxim (Berberidaceae), significantly relieves symptoms in patients with COPD. However, the mechanism of action remains unclear and further investigation is required to establish whether it may serve as an alternative or complementary therapy for COPD. The aim of the present study was to determine the effects of icariin in human bronchial epithelial cells exposed to cigarette smoke extract (CSE) and to determine whether icariin reverses GC resistance. The results revealed that icariin significantly increased the proliferation of CSE-exposed cells. Furthermore, icariin significantly increased protein expression of the anti-inflammatory factor interleukin (IL)-10 and significantly decreased protein expression of the pro-inflammatory factors IL-8 and tumor necrosis factor α. Icariin also attenuated the expression of the cellular matrix remodelling biomarkers matrix metallopeptidase 9 and tissue inhibitor of metalloproteinase 1, and decreased the production of reactive oxygen species (ROS). In addition, icariin regulated the expression of GC resistance-related factors, such as GC receptors, histone deacetylase 2, nuclear factor erythroid-2-related factor 2 and nuclear factor κ B. The results obtained in the present study suggested that icariin may decrease CSE-induced inflammation, airway remodelling and ROS production by mitigating GC resistance. In conclusion, icariin may potentially be used in combination with GCs to increase therapeutic efficacy and reduce GC resistance in COPD.