Background The number of Clare cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.Methods Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS+NAC group) oral intake of NAC 80 mg·kg~(-1)·d~(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The Mrna expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.Results Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3±14.7 vs. 53.7±11.5, P