We aimed at evaluating the effects of caffeic acid phenethyl ester (CAPE) on the histopathological changes in the lungs of rabbits exposed to cigarette smoke exposure. Four groups with six rabbits each were as follows: cigarette smoke group, CAPE group, cigarette smoke + CAPE group and control group. The cigarette smoke group was exposed to cigarette smoke 1 hr daily for 1 month. The CAPE group was administered intraperitoneal CAPE. The CAPE + cigarette smoke group was both exposed to cigarette smoke and was administered intraperitoneal CAPE. The control group was exposed to clean air. After 1 month, the rabbits were killed and the lung tissues were examined histopathologically. Peribronchial and intraparenchymal inflammation, intraparenchymal vascular congestion and thrombosis, intraparenchymal haemorrhage, respiratory epithelial proliferation, number of macrophages in the bronchiolar and alveolar lumen, alveolar destruction, emphysematous changes and bronchoalveolar haemorrhage scores were significantly higher in the cigarette smoke group than in the control group. Administration of CAPE to cigarette smoke-exposed rabbits significantly prevented all these changes. CAPE seems to have significant preventive effects on the severe histopathological changes in the lungs associated with cigarette smoke exposure. However, in some instances, it may not alter the progression to fibrosis.