Objective To investigate the effects of methylprednisolone on airway inflammation of chronic bronchitis in rats, and to explore its possible mechanism. Methods Forty SD rats were randomly divided into five groups, ie. a blank control group, amethylprednisolone control group, a model group, and two methylprednisolone intervention groups. Chronic bronchitis model was established by cigarette inhalation in the model group and two intervention groups. Methylprednisolone was injected intraperitoneally in the two intervention groups before exposing to cigarette smog ( at the dose of 1 mg/ kg and 10 mg/ kg, qd,respectively) . The protein expression of phosphodiesterase 4D ( PDE4D ) in trachea and lung samples was determined by immunohistochemical staining. The average optical density of positive staining of PDE4D was determined by image analysis technique and gray scale scanning. Bronchoalveolar lavage fluid ( BALF) was collected for total and differential cell counts, and the concentrations of TNF-αand interleukin-8 ( IL-8) in BALF were detected by ELISA. Results Cigarette smoking induced obvious airway inflammation in themodel group, and the inflammation was alleviated in the two methylprednisolone intervention groups.Compared with the two control groups, the expression of PDE4D was obviously elevated in tracheal and lungs in the model group( P lt; 0. 05) . Moreover, the increased expression of PDE4D was positively related with theincreased release of TNF-αand IL-8 in BALF. The expression of PDE4D and the release of TNF-αand IL-8 in BALF were decreased after the treatment with methylprednisolone in a dose-dependent manner ( P lt;0. 05) . Compare with the low dose intervention group, there was no markedly difference related to PMNnumber and TNF-α release in the high dose intervention group ( P gt; 0.05) . Conclusions Methylprednisolone may alleviate airway inflammation of chronic bronchitis by inhibiting the expression of PDE4D in rats. Inhibition of PDE4D may down-regulate TNF-αactivity, which may further reduce IL-8 release and alleviate airway inflammation.