Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic beta-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of beta-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value. The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats. (c) 2005 Elsevier Inc. All rights reserved.