The aim of this study was to investigate the protective effect of puerarin on attenuating caspase-3 expression in osteoblasts of streptozotocin-induced diabetic rats and the possible mechanisms involved. Diabetic rats were treated with a puerarin injection of 100 mg/kg/day. After 6 weeks, the bone mineral density, pathological changes and expression of caspase-3 were observed. The bone mineral density in the diabetic rats was significantly lower compared to the control group, while osteoblast numbers in the cortical bone were significantly reduced, and new bone formation in the diabetic rats was rare. Caspase-3 expression in the osteoblasts of diabetic rats increased compared to the rats in the control group. These pathological changes were improved and caspase-3 expression decreased in the puerarin-treated rats compared to the diabetic rats (P