Our understanding of the pathogenesis of diabetes, obesity and other metabolic disorders has benefited greatly from the use of dietary interventions and gene targeting methodology in mice to elucidate molecular mechanisms. However, such efforts are often hampered by a lack of facilities or expertise for metabolic phenotyping. The Mouse Phenotyping, Physiology and Metabolism Core provides investigators of the Penn Diabetes and Endocrinology Research Center (DRC) with access to state-of-the-art, timely and cost-effective resources for performing metabolic studies in mice. The core offers consultation and assistance with experimental design, and an expanding list of services including Comprehensive Laboratory Animal Monitoring System (CLAMS) that can simultaneously record energy expenditure, locomotor activity, eating and drinking, glucose and insulin clamp studies (including radioactive tracers for determining hepatic glucose output and uptake into other tissues), measurement of body composition using dual emission x-ray absorptiometry (DEXA) and nuclear magnetic resonance spectroscopy, thermal imaging, exercise capacity, and a variety of standard metabolic assays. In addition to the many existing services that have been critical to the productivity of DRC investigators, we are excited to be providing new services aimed at phenotyping in variably controlled conditions of ambient temperature and light, as well as facilitating metabolic flux studies through the development of “cold clamp” techniques for delivery of isotope-labeled metabolites while controlling glucose and insulin levels. Studies in the core are performed by two research specialists and a technical director under the leadership of Dr. Joseph Baur and coordinated with other core laboratories including the Biomarkers and Metabolomics cores. These efforts allow DRC investigators to rapidly translate ideas from the bench to mice as the first critical steps toward new therapeutic approaches for the multitude of patients suffering form diabetes and related disorders.