Excellent results are obtained with pancreas transplantation for the treatment of diabetes mellitus. The clinical parameters indicating graft dysfunction are nonspecific, and evaluation of a graft biopsy is often necessary to determine the etiology of graft dysfunction and assess the status of the graft. Inflammation of the pancreas allograft is the most common histological feature seen in core biopsies. In most cases, the inflammation is secondary to acute rejection, chronic rejection, and infectious complications. Although in many ways the morphological features of these processes overlap, there are also important differences that can help the pathologist to reach the correct diagnosis.