Experimental COPD is glucocorticoid-resistant. A–F, WT BALB/c mice were exposed to cigarette smoke or normal air for 12 weeks and were treated with dexamethasone or sham-treated with sterile distilled water either prophylactically throughout (Dex), or therapeutically (tDex) for the last 6 weeks, of the smoking protocol. Steroid treatment had no effect on (A) macrophage (M), neutrophil (N) and lymphocyte (L) numbers in the BALF, (B) alveolar enlargement or changes in lung function; (C) work of breathing, (D) total lung capacity (TLC), (E) functional residual capacity (FRC) or (F) forced expiratory volume in 100 milliseconds/forced vital capacity (FEV100/FVC) ratio. Data are means±SEM of 6–8 mice/group, # P<0.05, ## P<0.01, ### P<0.001 compared to mice that breathed normal air. There were no differences between other groups.