Introduction: Osteoporosis is a bone disease characterized by reduced bone mass, disrupted microarchitecture, and deteriorated bone strength, leading to increased fracture risk. The dysfunction of bone cells is associated with various factors, making it important to study the regulatory mechanisms of bone cells for prevention and treatment of osteoporosis. BMPR2 is a critical molecule in the BMP signaling pathway, regulating osteoblast proliferation, differentiation, and bone formation processes. Decreased BMPR2 expression is associated with osteoporosis, but its specific mechanisms are unclear. Materials and Methods: Twelve-week-old C57BL/6 mice were divided into experimental and control groups, with 10 mice in each group. The experimental group was injected with BMPR2 siRNA into the left tibia, while the control group was injected with PBS. Osteoblasts were isolated and cultured, and their proliferation and differentiation were detected using MTT assay and ALP staining. The experimental data were statistically analyzed using SPSS 20.0 software. Results: BMPR2 siRNA significantly reduced osteoblast proliferation (P<0.05) and differentiation (P<0.01). The bone density of the experimental group of mice was significantly decreased (P<0.01). Conclusion: BMPR2 plays an important role in the development and progression of osteoporosis, regulating osteoblast proliferation, differentiation, and bone formation processes. Targeting BMPR2 may provide new therapeutic strategies for the prevention and treatment of osteoporosis.