The present study was carried out to evaluate a unilateral hind limb immobilization model in the mouse. The right legs of male mice (age 10-12 weeks) were immobilized for 3 weeks against the abdomen by an elastic bandage. Body weight decreased significantly during the immobilization. Peripheral quantitative computed tomography (pQCT) analysis showed that the cross-sectional cortical area (CSA), the bone mineral content (BMC), and the bone mineral density (BMD) of the tibial diaphysis were lower in both legs of the immobilized animals than in age-matched controls, but the difference was mainly due to weight reduction. At the tibial metaphysis, CSA, BMC, and BMD were reduced in both legs of the immobilized animals, even after weight adjustment. At the femoral neck, CSA, BMC, and BMD were significantly lower in both legs of the immobilized animals, and the difference between the hind legs of the immobilized animals was also highly significant. The findings of the pQCT study were in good agreement with the changes in mechanical strength. The tibia was a more sensitive indicator of diaphyseal bone weakening than the femur when measuring the bending breaking force of the diaphysis. The femoral neck showed significantly decreased strength, and the difference between the immobilized leg and the contralateral leg was most clearly seen in lateral loading. We conclude that 3 weeks of hind limb immobilization weakened the tibia and femur significantly compared with their contralateral counterparts. The reduction was more significantly seen in the mechanical bending strength than in the pQCT evaluation, and the femoral neck was the most sensitive indicator of bone weakening.