Chronic idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune disease characterized by the production of antibodies against antigens on the membranes of platelets, resulting in enhanced destruction of the platelets by macrophages. Leptin, a cytokine-like hormone, plays a role in the pathogenesis of several autoimmune diseases. In this study, we observed significantly increased plasma leptin levels combined with decreased soluble leptin receptor (sOB-R) levels in 18 chronic ITP patients compared with 14 controls. We also demonstrated significantly elevated mRNA expression of long form leptin receptor (Ob-Rb) on peripheral blood mononuclear cells (PBMCs) from chronic ITP patients. Treatment with recombinant leptin or serum with high leptin levels enhanced in vitro secretion of IgG antiplatelet antibodies by splenocytes and PBMCs from patients with chronic ITP. After depletion of CD4(+) T cells from splenocytes, leptin lost this function. Further studies showed that leptin could increase platelet reactive T cells. These findings suggest that leptin may be involved in the pathogenesis of chronic ITP and might offer a potential target for the treatment of this disease.