Early lesions of systemic sclerosis (SSc) consist of altered endothelial cells (EC) function, perivascular infiltrating monocytes, and activated T cells adjacent to activated fibroblasts. The interactions among leukocytes, EC, and fibroblasts depend on expression and function of cell adhesion molecules and chemokines. The release of soluble cell adhesion molecules expressed on EC may represent the ongoing EC activation that correlates with some complications and early stages of SSc. Recently, chemokine abnormalities have been described in SSc, which might explain the altered accumulation of some leukocyte subsets in the affected tissues. Aberrant interactions between leukocytes and fibroblasts have also been reported. Thus, recent studies indicate that many steps of cell-cell interactions become dysregulated in SSc.