This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a prospective, open-label study in 10 type 1 diabetic participants receiving their first islet-only transplant. All participants will receive induction immunotherapy with hOKT3+[unreadable]1 (Ala-Ala), and rituximab. Maintenance immunosuppresion will be with sirolimus and tapered, low dose tacrolimus. The primary endpoint examines the efficacy of utilizing hOKT3+[unreadable]1 (Ala-Ala), and rituximab, induction with sirolimus and temporary tacrolimus maintenance immunosuppresion in reversing diabetes following 1 to 2 intraportal islet allotransplants and in maintaining adequate immunological protection of transplanted islets against both allo- and autoimmunity. More specifically, the primary endpoint examines the proportion of subjects with full islet transplant function (insulin independence;HbA1c 6.5%;and no episodes of severe hypoglycemia) at 1 year after the initial islet transplant. The secondary endpoint examines the safety of the regimen, i.e., the occurence of procedural complications and adverse events related to immunosuppressive, with particular emphasis on the cumulative incidence of malignancies, opportunistic infections, and other bacterial, fungal , and viral infections at 1 year after the islet transplant.