The capacity to record the spatial and quantitative distribution of cellular subtypes involved in diabetogenic processes is a key element in experimental diabetes research. A non-invasive technique to accurately monitor parameters such as pancreatic β-cell mass (BCM) and its distribution would provide a stepping stone in understanding different aspects of diabetes pathogenesis. It would also assist in the development of therapeutic regimes by providing a tool for the evaluation of anti-diabetic drugs or other curative or diagnostic measures. At present, a range of imaging modalities are being explored for this purpose. Whereas nuclear imaging techniques, characterised by their high tissue penetration depth but relatively low spatial resolution, appear most promising for the study of humans and large animals, optical imaging enables a route to cost-effective, high sensitivity, high resolution imaging in rodent models for disease. In this commentary, the potential impact of infrared fluorescent proteins (IFPs), as recently reported by Shu et al in Science, for imaging of the pancreas in small animals will be discussed.