Otitis media with effusion (OME) represents a spectrum of chronic disease states ranging from serous to mucoid otitis media. OME remains a common problem in the pediatric and geriatric population, but its etiology and pathogenesis are not fully understood. Several models using chinchillas, guinea pigs, and cats have been examined. In most of animal models, however, investigators are limited to the manipulation of experimental conditions and investigation of the individual relationships of various factors in the evolution of OME. In contrast, the mouse represents an ideal model for OME because of the availability of a wide variety of reagents. In this study, we made a murine model (BALB/c, male, 5 weeks) of long-term OME induced by a combination of injection with endotoxin into the bullae and eustachian tube blockage via an external surgical approach. Endotoxin induced effusion was produced using lipopolysaccharide from nonty peable Haemophilus influenzae. Mice were decapitated 3days, 2weeks, and 2months after surgery. In AB-PAS staining, compared to no treatment mice, the goblet cell population in the middle ear mucos a increased at 3 days and 2weeks after surgery in OME mice, but decreased significantly at 2months. In electron microscopy, the intracellular space was enlarged, and the tight junction complex was broken down in the animals at 2 months after surgery. This model should provide a necessary tool in the futher study of chronic OME.