Several studies have shown that transplantation of embryonic stem cells into diabetic animals either improved or normalized blood glucose levels. In this study, we examined the dose-dependent effect of early (prediabetic stage) intravenous administration of human umbilical cord blood (HUCB) mononuclear cells on blood glucose levels, survival, and insulitis in nonobese diabetic (NOD) mice with autoitnmune type 1 diabetes. The results show that mice treated with HUCB cells significantly lowered their blood glucose levels and increased their lifespan, as compared with untreated mice. Also, a significant reduction in insulitis was observed in treated than in untreated mice. The mice that received the highest dosage (200 x 10(6)) of cells had greater reduction in blood glucose levels and the degree of insulitis than the mice that received lower dosage (100-150 x 10(6)) of cells. Prolonged lifespan in the former group of mice seems to be related to better control of blood glucose levels. Thus, administration of HUCB cells in the prediabetic stage without any immunosuppression improves type 1 diabetes by protecting the islets from insulitis in NOD mice. (C) 2004 Elsevier Inc. All rights reserved.