INTRODUCTION: Diabetic osteoporosis (DOP) has gradually gained public attention. The clinical manifestations of DOP include bone mass loss, bone microstructural damage, and increased bone fragility. background: Diabetic osteoporosis (DOP) has gradually gained public attention. The clinical manifestations of DOP include bone mass loss, bone microstructural damage and increased bone fragility. Intracellular reactive oxygen species (ROS) production was significantly increased under high glucose (HG) conditions, with deleterious effects on bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Vitamin K2 (VK2) has been demonstrated to promote bone formation both in vitro and in vivo. However, its potential role in diabetes-induced osteoporosis remains unelucidated. METHOD: Intracellular reactive oxygen species (ROS) production was significantly increased under high glucose (HG) conditions, with deleterious effects on bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Vitamin K2 (VK2) has been demonstrated to promote bone formation both in vitro and in vivo. RESULT: However, its potential role in diabetes-induced osteoporosis remains unelucidated. This study aims to verify whether VK2 treatment could relieve the deleterious effects of high glucose on BMSCs and delay the progression of osteoporosis. The results revealed that the HG environment downregulated the expression of osteogenesis-related proteins. method: The protective effect of VK2 on BMSCs were evaluated by CCK-8, the mitochondrial function was detected by mitosox and JC-1. Osteogenic diferentiation potential was examined by alkaline phosphatase (ALP) staining and alizarin red s (ARS) staining.Simultaneously, we used an established diabetes-induced osteoporosis rat madel to assess the effects of VK2 in vivo. CONCLUSION: Correspondingly, VK2 treatment reversed the osteogenic phenotype of BMSCs under HG conditions. In addition, using an established diabetes-induced osteoporosis rat model, we found that VK2 administration could restore bone mass and microstructure. In conclusion, our results provide a promising therapeutic option in the clinical treatment of DOP. other: NO