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Objective. To assess histological changes of colonic mucosa in patients with clinically different types of irritable bowel syndrome (IBS) before and after the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor. Methods. Adult patients (over 18 years) with confirmed diagnosis of IBS were examined. Biopsy specimens were taken from colon during colonoscopy for the next histological examination. One expert gastrointestinal pathologist assessed all tissue samples. We patent semi quantitative assessment of the severity of cell infiltration of colonic mucosa, which could be assessed as inflammatory (neutrophils), immune (lymphocytes, plasma cells, macrophages), or allergic (eosinophils) response (0 to 3 degrees). All patients received treatment due to the clinical variant of IBS: 1) IBS-constipation – mirtazapinum 15 mg/night+lactulose 30ml/morning (+30ml/night if needed); 2) IBS-diarrhea – escitalopram 5mg/night+rifaximine 600mg/twice a day; 3) IBS-unspecified – mirtazapinum 15 mg/escitalopram 5mg/ night; 4) IBS-mixed – mirtazapinum 15 mg, lactulose 30ml/morning (+30ml/night if needed) / escitalopram 5mg/night+rifaximine 600mg/twice a day. Results. 107 patients were examined, 36 of them had constipation (I group), 35 – diarrhea (II group), 22- unspecified variant (III group) and 12 patients had mixed variant of IBS (IV group) due to Rome III criteria (2006). 1st degree of lymphocyte infiltration was detected in 100% IBS-constipation patients and in 58,3% IBS-mixed variant (p0.05). No cases of 2nd or 3rd degree of colonic mucosa infiltration were found. Conclusion. After the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor we found that the degree of inflammation of colonic mucosa was reduced or disappeared, due to the zero degree of infiltration according to our patented classification.