Objective：This study aims to construct osteoclast-special Trio gene knockout mouse model and explore the effects of Trio on osteoclasts. Methods：Osteoclast-special Trio gene knockout mice were cultivated by cre-loxp recombination system. Micro-CT was used to scan femurs. The histologic sections of femurs were stained with HE staining，and tartrate resistant acid phosphatase staining to observe number of osteoblasts and osteoclasts. Moue bone marrow cells were treated with macrophage colony stimulating factor（M-CSF） and receptor activator of nuclear factor-κ B ligand（RANKL） for differentiation to discover the effects of Trio on osteoclasts. Results：The mice of Trio knockout group showed small body size. The result of Micro-CT revealed bone mass and related indexes increased. Histologic sections staining displayed that the bone mass of femur increased and osteoclasts decreased in gene knockout mice. In vitro，the number of osteoclasts differentiated from bone marrow cells decreased in mice of Trio knockout group. Conclusion：osteoclast-specific Trio gene knockout mouse model was successfully established. The bone mass of Trio gene knockout mice increased，and osteoclast differentiation was inhibited.