<p>Background: Nowadays, transplantation of bone marrow-derived Mesenchymal Stromal Cells (BMSCs) is currently an important alternative therapy for patient&rsquo;s type 1 diabetes mellitus. But a number of critical obstacles lie ahead of this new strategy including reducing stem cell homing to the damaged tissue due to oxidative stress. The purpose of the present study was to investigate whether preconditioning of BMSCs with SDF-1 could enhance their homing to the pancreas and promote regeneration of the pancreatic &beta; cells after being intravenously injected.<br /> Methods: Mice BMSCs were isolated and expanded. Cell proliferation was assayed by MTT Assay. Preconditioning was performed with 10 <em>ng/ml</em> SDF-1&alpha; for 24 <em>hr</em>. Male NMRI mice were injected with high-dose STZ (150 <em>mg/kg</em>). The preconditioned or unpreconditioned BMSCs at a dose of 1&times;10⁶cells were infused via the tail vein. Blood and pancreatic tissue samples were taken from all mice for flow cytometry, biochemical and histological studies.<br /> Results: Proliferation and homing of BMSCs to the pancreas were significantly increased in the BMSCs with SDF-1&alpha; preconditioning. Differentiation of transplanted BMSCs, were significantly increased in preconditioning group. Although BMSCs without SDF-1 preconditioning exhibited remarkable recovery of pancreatic islets structure but this recovery were significantly increased in the BMSCs with SDF-1&alpha; preconditioning.<br /> Conclusion: Our results showed the effectiveness of SDF-1&alpha;preconditioning in BMSCs transplantation of STZ induced diabetes mice which might be achieved through improvement of BMSCs homing into the injured pancreas.</p>