ABSTRACT Visualizing and quantifying tissue and cellular pathologies are central to understanding the pathogenesis, progression, and complications of metabolic disease, and to monitor the effectiveness of its treatment. Methods of labeling, imaging, and quantifying cellular elements have improved rapidly and are providing new capabilities to evaluate phenotypes at the sub-cellular, cellular, and whole-organ levels. The Advanced Tissue Pathology and Imaging Core (ATPI) has been in great demand during the current funding cycle and has evolved significantly since the last submission to meet the changing needs of DRC investigators. The ATPI has proven broadly successful in achieving its mission of assisting individual investigators in histophenotyping. Originally conceived and organized as a histology core and subsequently expanded to include microscopy, the ATPI continues to evolve to meet the everchanging needs of DRC investigators. It was successfully reorganized and expanded during the current funding period to include state-of-the-art clearing, molecular “staining” and imaging technologies. To meet the large and growing demands for these services identified in investigator surveys and recommended by reviewers in the previous funding cycle, we streamlined the administrative components of the ATPI by creating an on-line service request system and increased efforts to provide the heaviest users with the access to equipment and training needed to perform many of the techniques for themselves. An expert in the implementation of these advanced techniques in both the brain and peripheral organs, Dr. Lori Zeltser has led the restructuring of the Core. The ATPI services complement those provided by other DRC Cores, so that investigators who take advantage of DRC resources can fully characterize the histologic, immunologic, and metabolic function and phenotypes of mice. Thus, the combined investments by Columbia, the Naomi Berrie Diabetes Center and the DRC have been leveraged to provide excellent services at low costs.