There is a growing evidence that molecular and cellular mechanisms may play a role in pathogenesis in chronic otitis media.was to determine the intensity of apoptosis in granulation tissue in chronic otitis media.Fifty four patients with chronic otitis media, who underwent surgical treatment, were enrolled into the study. The apoptosis was measured in paraffin-embedded granulation tissue specimens by an immunohistochemical methods, by staining with a monoclonal antibody against apo-1/Fas/CD95 and P53 protein. The bacteriological evaluation of middle ear discharges were also done.It was found statistically significant difference in expression of apo-1/Fas antigen between the groups with good clinical course (good healing and without recurrence) than those in the group with poor healing and recurrence (mean percentage of immunopositive cells 1,52 vs 3,34 respectively, p<0,001). The activity of apo-1/Fas antigen was more intense in tissue samples from the group with bacterial infection caused by Pseudomonas aeruginosa/Proteus sp/Staphyloccocus MRSA than those in the group without this infection (mean percentage of immunopositive cells 3,78 vs 1,75 respectively, p<0,001). The differences were also observed for P53 protein expression between the same groups, however they were not significant. There were no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media. The significant negative correlation was found between expression of apo-1/Fas antigen and expression of P53 protein (r = −0,64, p<0,001).In granulation tissue in chronic otitis media different expression of apo-1/Fas antigen was found in relationship to clinical course of disease and bacterial infection caused by Pseudomonas aeruginosa/Proteus sp/Staphyloccocus MRSA. It may suggest that apoptosis mediated by apo-1/Fas mechanism may contribute to pathogenesis of chronic otitis media.