Psoriasis vulgaris is a systemic Th1 cytokine-mediated skin disease. In psoriatic epidermis, the leading change is proliferation of keratinocytes associated with inflammation. The role of immunologic reactions is obvious through the presence of many activated T lymphocytes in epidermis and dermis and also association with HLA class I antigen. Stimulation of T lymphocytes in epidermis by peptide antigens presented in connection with HLA class I molecules is assumed to be the key event in immune response (CD4 and CD8) activation. Activated T lymphocytes secret many cytokines that stimulate keratinocyte proliferation such as interleukin 2 -IL-2, γ interferon -IFN-γ, tumor necrosis factor α -TNF-α, interleukin 6 -IL-6. Recent research data suggest the significance of adhesion molecules ICAM-1 and VCAM-1 in the development of psoriasis. In this study we have shown their expression in psoriatic lesional and non-lesional skin. During the last ten years immunotherapy with monoclonal antibodies directed against molecules involved in immunologic process has been used successfully in these patients. Aim The aim of this study was to determine the presence of activated T lymphocytes, macrophage 68 and adhesion molecules: intercellular adhesion molecule-1 (ICAM- 1), vascular adhesion molecule-1 (VCAM-1) and interleukin-2 receptor (IL-2R) in lesional and non-lesional psoriatic skin as compared with healthy skin in control group in order to evaluate the possible differences as compared with healthy skin and determine the role of adhesion molecules in etiopathogenesis of psoriasis. Materials and methods Skin biopsies of lesional and non-lesional skin at least 5 cm from lesion were performed in 50 patients with psoriasis that have used no topical or systemic therapy during at least two weeks prior biopsy. Skin biopsies of healthy skin were performed in 50 healthy volunteers. All fresh frozen sections were examined histologically and immunohistochemically at the Department of Pathology Medical Faculty University of Rijeka. Standard immunohistochemical procedure using DAKO kits and IL-2R kit of Medical Faculty University of Rijeka followed by the molecule expression reading in order to evaluate the expression of lymphocyte markers, IL-2R and adhesion molecules (Olympus BX 51). Statistical analyses were performed at Medical Faculty University of Rijeka. Results We have detected statistically significant difference of ICAM-1 expression in lesional and non-lesional skin in psoriatic patients (p<0,001) in comparison with healthy skin of our volunteers. Also, we have found statistically significant difference in adhesion molecule VCAM-1 expression in comparison with healthy volunteers (p<0,0001). Significant difference was detected in IL-2R expression between lesional psoriatic skin and healthy skin of examined volunteers (p<0,001). CD4 and CD8 lymphocytes were found in epidermis and dermis in augmented number in lesional skin of psoriatic patients as compared with healthy volunteers (p<0,001). Also, increased expression of CD68+ molecule, a macrophages marker, was found in lesional skin of psoriatic patients in comparison with skin of healthy volunteers (p<0,001). Conclusion According to obtained results and previously published studies, we have established a significant difference in expression of adhesion molecules between lesional skin and in non-lesional skin of psoriatic patients in comparison with healthy skin. These results prove their importance in etiopathogenesis and immunologic events involved in development of psoriatic lesions. It is important to emphasize that non-lesional skin in psoriatic patients is in «stand by» position and in each moment could become lesional, due to high levels of adhesion molecules expressed in non-lesional skin of these patients. We can assume that targeted biologic therapy with specific monoclonal antibodies could improve the treatment of psoriasis vulgaris.