Objective In terms of the TLR/ NF-κB signaling pathway, we explored the effect of Bushen Yiqi Huayu granules on the formation of blood vessels in osteoporotic rats. Methods Sixty SPF female SD rats were randomly divided into sham operation, model, granule and positive control groups with 15 rats in each group. Except for the sham operation group, the other three groups were subjected to bilateral ovarian extraction to prepare an osteoporotic model. The sham operation group underwent surgery only without removing the ovaries as a control. Rats in the granule group were administered 5 g / kg Bushen Yiqi Huayu granules by gavage, rats in the positive control group were administered 0. 5 mg / kg alendronate sodium tablets by gavage, and rats in model and sham operation groups were administered a gavage with the same amount of normal saline. After 12 weeks of continuous administration, the rats were sacrificed. Femoral tissues of the rats were subjected to bone density testing, HE staining, Micro-CT three-dimensional reconstruction analysis, CD31 fluorescence immunoassay, and blood perfusion imaging analysis. Serum VEGF and HIF-1α concentrations were measured by ELISA. Western blot was used to detect expression of p50 / p-p50 and p65 / p-p65 protein. Results Compared with the sham operation group, rats in the model group had a low bone density (P< 0. 05), trabecular bone growth was sparse, blood vessel formation was slower, the number of blood vessels was smaller, serum VEGF and HIF-1α concentrations were significantly decreased (P<0. 05), and expression of p50 / p-p50 and p65 / p-p65 proteins in femoral tissues was increased significantly. Compared with the model group, the trabeculae of rats in granule and positive control groups grew well, the number of blood vessels was formed, bone density was increased significantly, serum levels of VEGF and HIF-1α were increased significantly (P<0. 05), and the protein levels of p50 / p-p50 and p65 / p-p65 were decreased significantly (P< 0. 05). Conclusions Bushen Yiqi Huayu granules may promote the angiogenesis in osteoporotic rats by regulating the TLR/ NF-κB signaling pathway and plays an important role in alleviating osteoporosis.