Leptin, the adipocyte-secreted hormone, exerts its main function as regulator of food intake and energy expenditure through central effects at the hypothalamic level. However, it appeared that this cytokine-like peptide has also direct effects on other peripheral tissues and cell types. Remarkable effects have been demonstrated on the immune function in vivo and in vitro. Monocytes are one of the target cells of leptin, and we have demonstrated that secretion of L-1Ra, an IL-1 receptor antagonist, is induced by leptin. In human obesity leptin and IL-1Ra levels are elevated, and these levels are decreased after weight loss. It is discussed that IL-1Ra may contribute to central leptin resistance.