Uncoupling proteins (UCPs) located in the inner mitochondrial membrane are involved in the regulation of energy balance. Thus far, 5 UCP isoforms have been identified, but controversies exist in the research focused on the function of the UCPs (except UCP1) in the pathogenesis of obesity. Because of the known cross-reactivity of the antibodies presently available for the detection of UCP proteins, this study systematically analyzed the differential tissue expression profiles of the 5 UCP isoforms in lean control mice and ob/ob mice by using real-time polymerase chain reaction (PCR) analysis. The results show that the tissue-specific expression patterns of individual isoforms in normal and ob/ob mice are considerably different; this will provide new insights into the functions of UCPs in the pathogenesis of genetic obesity.