Objective: Although current obesity therapies produce some benefits, there is a need for new strategies to treat obesity. A novel proposal is the use of anti-idiotypic antibodies as surrogate ligands or hormones. These anti-idiotypic antibodies carry an internal motif that imitates or mimics an epitope in the antigen (i.e., hormone or ligand). Thus, anti-idiotypic antibodies to several ligands may mimic them in transducing signals when binding to their receptors. Research Methods and Procedures: We developed an anti-idiotypic polyclonal antibody against the region of a leptin monoclonal antibody that competitively binds leptin, mimicking the active site structure of leptin. To test whether our anti-idiotype could also reproduce leptin functions, we examined food intake, body weight, and colonic temperature in male Wistar rats (n = 9) in response to intracerebroventricular administration of the leptin anti-idiotype. Results: Our leptin anti-idiotype induced a significant reduction in food intake coupled with an increase in body temperature comparable to that of leptin. That is, the intracerebroventricular administration of 8.0 microg of leptin anti-idiotype or 5.0 microg leptin significantly increased colonic temperature (Delta 1.9 plusminus 0.11 °C and Delta1.7 plusminus 0.12 °C, respectively). In addition, both decreased 24-hour food intake (-26.4 plusminus 2.4% and -21.9 plusminus 2.2%) compared with the control. The gain in body weight was also decreased by acute administration of the anti-idiotype (-1.4 plusminus 0.28%) and leptin (-1.1 plusminus 0.17%) vs. the phosphate-buffered saline control (1.3 plusminus 0.15%). Discussion: These studies revealed that the leptin anti-idiotype inhibited food intake and enhanced heat production, mimicking leptin's central actions.