Type 1 diabetes mellitus is characterized by the destruction of pancreatic islet beta cells, which leads to insulin insuffi-ciency, hyperglycemia, and reduced metabolic glucose level. Insulin replacement is the current standard therapy for type 1 diabetes mellitus but has several limitations. Pancreatic islet transplantation can result in the production of exogenous insulin, but its use is limited by immune-rejection and donor availability. Recent studies have shown that mesenchymal stem cells (MSCs) can trans-differentiate into insulin-producing cells (IPCs), which could be utilized for diabetes mellitus treatment. Previously published re-ports have demonstrated that MSC or IPC transplantation could produce significant improvement in mouse models of diabetes mellitus. This study was aimed at determining the effects of two different methods of MSC transplantation on the efficacy of diabe-tes mellitus treatment in mouse models. The MSCs were isolated from umbilical cord blood and were proliferated following a pre-viously published procedure. Diabetes mellitus was induced in mice by streptozotocin (STZ) injection. Thirty days after transplan-tation, the weight of the mice treated by intra-venous infusion and intra-pancreatic injection was found to be 22% and 14% higher than that of the un-treated mice. The blood glucose concentrations in both intra-venous infusion and intra-pancreatic injection groups decreased and remained more stable than those in the control group. Moreover, insulin was detected in the serum of the treated mice, and the pancreas also showed gradual recovery. Based on the results of this preliminary investigation, intra-venous in-fusion seems more suitable than intra-pancreatic injection for MSC transplantation for diabetes mellitus treatment.