Abstract：Objective：To observe the effect of puerarin on bone mineral density and oxidative stress in mice with diabetic osteoporosis(DOP). Methods ： A total of 45 KKAy mice were given high-glucose/ high- fat diet and intraperitoneal injection with streptozotocin to establish a DOP model. After successful modeling，the mice were randomly divided into the model group，the metformin group and the puerarin group， with 15 mice in each group. Another 15 C57BL/6J mice were taken as the control group. After eight-week treatment， the levels of bone mineral density(BMD)， glucose metabolism indexes including fasting blood glucose(FBG)， glycosylated hemoglobin(HbA1c) and fasting insulin(FINS)， malondialdehyde (MDA)，catalase(CAT)，superoxide dismutase(SOD) ，8-hydroxydeoxyguanosine(8-OHDG)，osteopontin (OPN) and transforming growth factor- β(TGF- β) were observed； hematoxylin- eosin staining(HE) was used to observe the pathological changes in pancreatic tissue in mice； real- time reverse transcriptionpolymerase chain reaction(RT- PCR) and Western Blot were used to respectively detect the mRNA and protein expressions of bone morphogenetic protein- 6(BMP-6) and vascular endothelial growth factor (VEGF). Results：Compared with the control group，the levels of BMD，FINS，CAT and SOD in the model group were significantly decreased(P＜0.05)， and the levels of FBG， HbA1c， MDA， 8- OHDG， OPN， TGF- β and the mRNA and protein expressions of BMP-6 and VEGF in pancreatic tissue were significantly increased(P＜0.05)；in the model group，the pancreatic tissue was disordered，the intercellular space was widened，a large number of neutrophils were visible，and the nucleus was damaged. Compared with the model group， the levels of BMD， FINS， CAT and SOD in the metformin group and the puerarin group were significantly increased(P ＜ 0.05) ， and the levels of FBG ， HbA1c ， MDA ， 8- OHDG， OPN， TGF-β and the mRNA and protein expressions of BMP-6 and VEGF in pancreatic tissue were significantly decreased(P＜0.05)；after the intervention，the degree of pancreatic tissue injury in mice in the metformin group and the puerarin group was significantly improved. Conclusion：Puerarin has effects in regulating the mRNA and protein expressions of BMP-6 and VEGF in pancreatic tissue of DOP mice，improving BMD and reduce oxidative stress injury.