Abstract: Chimeric leptin which are proteins comprising leptin or a mutant or a variant thereof fused to a human immunogobulin domain. One favoured immunoglobulin domain is the human immunoglobulin Fc domain. The chimeric derivatives of leptin have, despite their large molecular size, good pharmacological activity combined with prolonged clearance rates. These derivatives of leptin are therefore indicated to be particularly useful for the treatment or prophylaxis of obesity or diseases and conditions associated with obesity such as atherosclerosis, hypertension and type II diabetes.