Objective To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) on rheumatoid arthritis and secondary bone loss in a spontaneous rheumatoid arthritis mouse model (Tg-huTNFα mice). Methods 3-week-old Tg-huTNFα mice were divided into three groups: ( 1) Model group: 0. 1 mL/10 g normal saline was intraperitoneally injected once a week; (2) huTNFα antibody intervention group (Anti-huTNFα): 10 mg/ kg Anti-huTNFα was intraperitoneally injected once a week; (3) BMSC intervention group (BMSCs): 5 × 10⁶ BMSCs were injected into both knee joint cavities once a week. During the intervention period, the animals were weighed once a week, and ankle joint health was scored clinically. The animals were killed after 10 weeks of intervention. The percentages of T cells, B cells and CD4⁺ / CD8⁺ T cells in the peripheral blood were analyzed by flow cytometry. The amounts of huTNFα, IL-4 and IL-1β in peripheral blood serum were detected by liquid chip technique. Pathological changes to the left knee joint and ankle joint were evaluated by HE staining, and the right femur bone structure was analyzed by bone histomorphometry. Results BMSCs and Anti-huTNFα provided relief from weight loss in Tg-huTNFα mice; inhibited joint swelling and deformation; and reduced the peripheral blood huTNFα content, joint pathology score, and extent of joint synovium and cartilage damage. Additionally, BMSCs improved the trabecular bone number and percentage trabecular bone area to different degrees and improved the femur bone structure in Tg-huTNFα mice. Conclusions Injection of BMSCs into the joint cavity significantly alleviated symptoms of rheumatoid arthritis in Tg-huTNFα mice, improved femur bone structure, and alleviated bone loss secondary to RA.