Objective To investigate the protective effect of salidroside ( SDS) on type 2 diabetic osteoporosis (DOP) rats and its influence on the forkhead box transcription factor O1 (FoxO1) / β-catenin pathway. Methods The rat model of DOP was established by feeding rats a high glucose and high fat diet for 8 weeks, injecting the rats with 30 mg / kg streptozotocin (STZ) intraperitoneally after 8 weeks, and then resecting the ovaries under sterile conditions in the 10th week. After successful modeling, the rats were randomly divided into model group, SDS group, and FoxO1 agonist group, with eight rats in each group; the eight rats in the normal group were fed a normal diet for the same length of time as for the other groups. On the second day after establishing the model, the rats in the SDS group were given 36 mg / (kg·d) SDS by gavage, and the rats in the FoxO1 agonist group were given 40 mg / (kg·d) resveratrol (Res) by gavage, for 11 weeks. The fasting blood glucose concentration was measured using a glucometer. the morphology of the femur was evaluated by hematoxylin & eosin (HE) staining, and femoral bone mineral was measured by dual energy X-ray absorptiometry. the serum concentrations of reactive oxygen species (ROS), superoxide dismutase ( SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detecte by ROS, SOD, MDA kits, respectively; and the concentrations of FoxO1 and β-catenin proteins in the femur were detected by Western blot. Results After modeling and before administration, compared with the normal group, the fasting blood glucose concentration was higher in the model group, SDS group and FoxO1 agonist group (P< 0. 05). After administration, the bone trabeculae of rats in the model group showed obvious fracture, serious damage, and reduced number; the bone trabeculae of rats in the SDS group and FoxO1 agonist group showed obvious fracture, but the trabecular space was reduced, and the trabecular number was increased. Compared with the normal group, the fasting blood glucose and serum ROS and MDA concentrations were higher in the model group (P< 0. 05), while the femoral bone mineral density, serum SOD and GSH-Px concentrations, and FoxO1 and β-catenin concentrations in the femur were lower (P< 0. 05). Compared with the model group, the fasting blood glucose and serum ROS and MDA concentrations were lower in the SDS group and FoxO1 agonist group (P< 0. 05), while the femoral bone mineral density, and serum SOD and GSH-Px concentrations, and femoral FoxO1 and β-catenin concentrations in the femur were higher (P< 0. 05). Conclusions SDS can activate the FoxO1 / β-catenin pathway, enhance antioxidant stress, and protect DOP rats.