Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA). Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model. Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250μg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage. Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome.