OBJECTIVE It is generally accepted that cigarette smoke is a major risk factor for middle ear disease. However, the literature is void of articles addressing the direct relationship between cigarette smoke exposure and middle ear disease. Furthermore, there are many conflicting opinions concerning the role of cigarette smoke in the pathogenesis of middle ear disease. The purpose of this study was to evaluate the effects of cigarette smoke on the Eustachian tube mucosa. METHODS Thirty healthy 150 to 230 g Sprague Dawley rats with normal middle ears were used. The animals were divided into six groups of five. Five experimental groups (N=5 each) were exposed to a domestic cigarette (This, tar 7.0 mg, nicotine 0.75 mg) every 30 minutes (total 2.5 hours, 5 cigarettes total) on a daily basis in a smoking chamber for 1, 2, 4, 6, or 8 weeks. A control group (N=5) was placed in the same chamber without exposure to cigarette smoke. After exposure, the animals were sacrificed and cross sections of the Eustachian tubes were prepared. Histologic changes of the Eustachian tube mucosa were observed through light and electron microscopes. RESULTS Loss of cilia, goblet cell depletion, and squamous metaplasia of the Eustachian tube mucosa were observed following exposure to smoke. The one- and two-week exposure groups demonstrated the greatest decrease in goblet cell counts. The eight-week exposure group showed recovery from this decrease. Squamous metaplasia was observed in all experimental groups and was most prominent in the eight-week exposure group. CONCLUSIONS These findings suggest that cigarette smoke directly affects Eustachian tube mucosa in the early stages of exposure. Some of the mucosal changes, however, were reversed during the latter stages of exposure. A mechanism different from that which occurs in the nasal cavity and trachea may be activated in the Eustachian tube after exposure to passive smoke. The protective function of the Eustachian tube may play some role in this mechanism.