Abstract: Objective To study the mechanism of bone marrow mesenchymal stem cells (BMSC) transplantation in promoting β-cell regeneration in diabetic model of SD rats. Methods Three days after a single high streptozotocin (STZ) dose (65 mg/kg) was injected into normal SD rats, their blood glucose levels were measured.Those with their blood glucose level> 28 mmol/L for 3 consecutive days were randomly divided into control group (n=15), BMSC transplantation group (n=15), BMSC supernatant transplantation group (n=15), and BMSC (marked with Dil stain) trace group (n=5). Results The blood glucose level was signif icantly lower (20.4±0.98 mmol/L, 26.2±1.53 mmol/L), the serum insulin level was signif icantly higher (0.99±0.23 ng/ml, 0.341±0.08 ng/ml), and the β cells regenerated faster in BMSC transplantation group and BMSC supernatant transplantation group than in control group 30 days after BMSC transplantation and after BMSC supernatant transplantation containing BMSC secreting factors.A small number of BMSC was detected but no co-marker of BMSC and insulin was detected in pancreas tissues of diabetic rats. Conclusion The secretion effect of BMSC is the mechanism of BMSC in promoting β-cell regeneration in diabetic rats.