【Abstract】 Objective To investigate the effect of different administration ways of glucocorticoid in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods One hundred and fifty patients with AECOPD (grade B and C) were randomly divided into intravenous administration group, oral administration group and aerosol inhalation group. Arterial blood gas (ABG) indexes (PO2 and PCO2), lung functions (FVC, FEV1 and FEV1/FVC), the serum levels of inflammatory mediators (CRP, TNFα, IL5, IL6 and IL10) and the adverse reactions were recorded, before and after 7 days treatment. Results After 7 days treatment, ABG indexes, lung functions and the serum levels of inflammatory mediators were all improved in 3 groups (P < 005 in all), compared with before treatment. Then, after 7 days treatment, the differences in the serum levels of CRP, TNFα, IL5, IL6 and IL10, and, FVC, PaO2 and PaCO2 were not found among 3 groups (P > 005 in all). However, the improvement of FEV1% and FEV1/FVC was more significant in intravenous administration group (P < 005 in all). And no differences in FEV1% and FEV1/FVC was observed between oral administration group and aerosol inhalation group (P > 005 in all), after 7 days treatment. Meanwhile, we also noticed that the rates of adverse reactions was lower in aerosol inhalation group (P < 005). And there was no difference in the rates of adverse reactions between intravenous administration group and oral administration group (P > 005). Conclusion Our results indicated that both systemic and inhaled corticosteroids could improve ABG indexes, lung functions and the serum levels of inflammatory mediators in patients with AECOPD. Meanwhile, the effects of intravenous administration of corticosteroid are better than that of oral administration and inhalation. However, inhalation was safer. Therefore, individual treatment should be considered in patient with AECOPD.