Scleroderma is a connective tissue disease characterized by involvement of small and large blood vessels, inflammation, autoimmune and histic reconstruction of the tissue. In this review the authors discuss the issues of cell-mediated and humoral immune response in this disease. Activation of CD4(+)T-lymphocytes and macrophages is considered to be an early marker of the onset of immune response, contributing to the fibrosis process and formation of antibodies. In these circumstances the interaction of immune system cells occurs due to bioactive substances produced by these cells (cytokines, interleukins). The issues regarding the influence of certain cytokines, such as IL-1, IL-2, IL-4, IL-6 and IL-8 interleukins and CD40-CD154 molecule on the development of sclerosis are discussed. There is evidence of a new subpopulation of T-lymphocytes (T-helper 17 cells) that produce IL-17, a proinflammatory cytokine that has a pleiotropic effect on fibroblasts, keratinocytes, endothelial cells, neutrophils, and memory T cells. The information on the role of other interleukins (IL-13, -15, -17, -18, -22) and growth factors in the pathogenesis of scleroderma is provided. Some of them can act as indicators of severity of the disease and/or skin fibrosis and/or systemic inflammatory and/or autoimmune processes.