Castration was used to establish the rat models of osteoporosis. A total of 30 rats were randomly divided into sham operation group， model group and Sal group （given with 40 mg·kg^－1 Sal by intraperitoneal injection once two days 4 weeks after modeling for 4 weeks）.HE staining method was used to observe the pathomorphology of femur tissue of the rats in various groups； dual-energy X-ray bone densitometer was used to detect the femur bone mineral density （BMD） of the rats in various groups； three-point bending test was used to detect the maximum loads of femur of the rats in various groups. In in vitro experiment， 30 μg·L^－1 macrophage colony stimulating factor （M-CSF） and 100 μg·L^－1 nuclear factor kappa B （NF-κB） ligand （RANKL） were used to induce the differentiation of bone marrow macrophages （BMMs）. The cells were divided into control group， RANKL group， RANKL +Sal group （10 mg·L^－1 Sal）， RANKL +Sal +vector group （10 mg·L^－1 Sal and 2 mg·L^－1 empty vector）， RANKL +Sal +LV-FKBP1A group ［10 mg·L^－1 Sal and 2 mg·L^－1 lentivirus-mediated FKBP1A overexpression vector （LV-FKBP1A）］， RANKL +Sal+LV-FKBP1A+QNZ group （10 mg·L^－1 Sal， 2 mg·L^－1LV-FKBP1A and 10 nmol·L^－1 NF-κB inhibitor QNZ）. MTT assay was used to detect the proliferation activities of the cells in various groups； flow cytometry was used to detect the apoptotic rates of cells in various groups； Co-IP experiment was used to verify the interaction between SMAD2 and FKBP1A； Western blotting method was used to detect the expression levels of SMAD family member 2 （SMAD2）， FK506-binding protein 1A （FKBP1A） and phosphorylated NF-κB P65 （p-P65） proteins in rat bone tissue and cells in various groups. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tartrate-resistant acid phosphatase 5b （TRAP5b） in serum of the rats and cells in various groups；real-time fluorescence quantitative PCR （RT-qPCR） was used to detect the expression levels of cathepsin K （CTSK） and calcitonin receptor （CTR） mRNA in bone tissue of the rats and cells in various groups.

The in vivo experimental results showed that compared with model group， the number of bone trabeculae in Sal group， the BMD and the maximum load of femur of the rats were significantly increased （P<0.01）， and the level of TRAP5b in serum was decreased（P<0.01）， the expression levels of SMAD2 and FKBP1A proteins and CTSK and CTR mRNA in bone tissue were significantly reduced （P<0.01）. The Co-IP experiment results confirmed that SMAD2 interacted with FKBP1A protein. The in vitro experimental results showed that compared with RANKL group， the proliferation activity of cells in RANKL+Sal group was significantly decreased（P<0.01），the apoptotic rate was significantly increased（P<0.01），and the TRAP5b level and the expression levels of SMAD2， FKBP1A and p-P65 proteins and CTSK and CTR mRNA were significantly reduced （P<0.01）.Compared with RANKL+ Sal +vector group，the apoptotic rate in RANKL+Sal+LV-FKBP1A group was significantly reduced（P<0.01），and the TRAP5b level and the expression levels of SMAD2， FKBP1A and p-P65 proteins and CTSK and CTR mRNA in the cells were significantly increased （P<0.01）.Compared with RANKL+ Sal+LV-FKBP1A group，the apoptotic rate in RANKL +Sal +LV-FKBP1A +QNZ group was significantly increased （P<0.01），and the TRAP5b level and the expression levels of SMAD2， FKBP1A and p-P65 proteins and CTSK and CTR mRNA in the cells were significantly reduced （P<0.01）.

Sal inhibits the activation of NF-κB by regulating the interaction between SMAD2 and FKBP1A protein， and alleviates the osteoporosis in the rats.