Type 1 diabetes is an autoimmune disease that kills the insulin producing beta cells of the pancreas. Our laboratory studies the mechanisms that lead to this destruction, and develops protocols for therapy to cure the disease. In our work we regularly make use of experimental mice, especially the non obese diabetic (NOD) mouse. One obstacle in our work is the location of the islets inside the pancreas, making it difficult to access them to assess immune infiltration and beta cell function without killing the mouse. We have developed a protocol that allows us to image infiltration in islets before, during and after treatment with immunomodulatory agents using multiphoton microscopy on islets grafted into the pinna of the ear. We have established that islets can be grafted into the pinna of the ear, and can continue to produce insulin and glucagon there. Furthermore, infiltration into islets grafted into the pinna of the ear can be detected and recorded in vivo using multiphoton imaging. Longitudinal imaging of islets grafted into the pinna can be used to determine immune infiltration in islets before, during and after treatment with immunomodulatory substances. This has allowed us to follow the resolution of immune infiltration after treatment with aglycosyl anti-CD3 antibody, and holds great potential for future studies of immune intervention as well as beta cell differentiation and function.