Background: Psoriasis is a T-cell mediated autoimmune disease. The objective of this work was to investigate the presence of cellular and soluble activation molecules in the blood of patients with psoriasis, not responding to local treatment and to study the effect of cyclosporin A (CsA) on these markers. Methods: Twenty-seven patients and 30 healthy controls were included in the study. The results were evaluated at baseline and at 15 days, 3, 6 and 12 months following initiation of treatment. Results: We found increased baseline values of lymphocytes and cells expressing the marker CD3+CD25+, CD54+ (ICAM-1) and CD58+ (LFA-3). Following CsA treatment, a significant decrease in the percentage of activated T cells expressing CD3+CD25+ and CD3+HLA-DR+ was noted at 6 and 12 months. Among the soluble factors studied, increased baseline serum levels of sIL-2R, sCD23 and neopterin were observed. CsA significantly reduced the levels of sIL-2R and IL-12. Conclusion: Although there is evidence for systemic immune activation in psoriasis, sIL-2R is the most consistently increased activation marker, related to the Th1 immune response, that may be used as a marker for monitoring disease activity and response to treatment with CsA in psoriatic patients.