Metabolic effects of immunosuppressive agents are of great importance in pancreas or islet transplantation. The aim of our study was to compare effects of tacrolimus-based immunosuppression in conjunction with sirolimus (RAPA) versus mycophenolate mofetil (MMF) on glucose metabolism in type 1 diabetic recipients following a simultaneous pancreas and kidney transplantation (SPK). We examined 30 insulin-independent patients after SPK with venous systemic drainage of the pancreatic graft. All recipients had good kidney graft function. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA(lc)), standard intravenous glucose tolerance test (IVGTT), and trough RAPA levels were assessed in pancreas recipients before elective steroid withdrawal. Insulin sensitivity was evaluated using the homeostasis model assessment (HOMA-IR). The groups did not differ in age, BMI, posttransplant period, steroid daily dose, HbA(lc), and fasting glycemia. We did not find any significant difference in the IVGTT response. Area under the curve of insulin levels during IVGTT and HOMA-IR were significantly lower in the RAPA group. Trough levels of RAPA had no significant impact on any of the examined parameters. Glucose tolerance measured with the use of IVGTT was similar in patients treated with RAPA and MMF. However, recipients on sirolimus treatment had significantly lower insulinemia during the test and consequently more favorable indices of insulin action as assessed by HOMA-IR.