Type 2 diabetes mellitus is a common problem in patients after solid organ transplantation. We studied the safety and efficacy of pioglitazone therapy in this setting. Ten patients with diabetes mellitus treated with insulin or glyburide after transplantation were studied after the addition of the thiazolidinedione pioglitazone. Serum creatinine, HBA1C, total daily insulin dose, tacrolimus dose, tacrolimus level and prednisone dose were followed for a mean of 242 days and compared to the corresponding values measured before the initiation of pioglitazone. The addition of pioglitazone caused no significant changes in serum creatinine or mean tacrolimus dose, and caused decreases in HBA1C (8.36%+/- 1.5% pre-pioglitazone, 7.08%+/- 1.5% post-pioglitazone, p = 0.018) and total daily insulin dose (125.1 +/- 28.1 units pre-pioglitazone, 80.6 +/- 22.8 units post-pioglitazone, p = 0.002). Our preliminary study suggests that pioglitazone is a safe and effective oral agent for the management of diabetes mellitus after transplantation.