The exact chronology of human otitis media is not clearly known ; however, experimental otitis media in animal models provides an excellent opportunity to assess a continum of changes of one type into another type of otitis media. We would like to discuss pathologic findings and a few enzymatic profiles of human and experimental animal otitis media to help understanding pathogenesis of otitis media. There were similarities between human and experimental otitis media induced by Pseudomonas aeruginosa in terms of pathological findings. Granulation tissue is primary pathological lesion of otitis media. Bone erosion or new bone formation were also found in both human otitis media and experimental otitis media. It has been known that complex biochemical events take place in the middle ear when the inflammation is developed. In human the lysozyme activity is related to the severity of the inflammatory reaction of the tissues. Thus the lysozyme activity may indicate the severity of inflammatory changes of the middle ear cavity. In animal studies of acute otitis media, the lysozyme levels of middle ear mucosa appear to reflect the mucosal pathology and the presence of bacteria and inflammatory cells. The PZ-peptidase level of human tissue is generally high in active inflammatory tissue, and also in specimens containing cutaneous tissue like cholesteatoma epithelium and normal skin. The PZ-peptidase levels in the mucosa of the Pseudomonas animal model suggest that local production of this enzyme in mucoperiosteal layer appears to increase with time after infection was induced. The results of the present study suggest the important role of collagenolytic enzyme such as PZ-peptidase in the natural course and development of complications of acute and chronic otitis media.