Objective To observe the changes of bone mass in reloaded rats after tail-suspension, and the effect and mechanism of simvastatin on this process. Methods Twenty-four 5-month old rats were divided into 4 groups of 6 animals in each group: Control (CL) group without tail-suspension, unloaded (UL) group with tail-suspension for 6 weeks, other 12 rats received tail-suspension for 3 weeks, then reloaded for subsequent 3 weeks (UL+RL) or combined with simvastatin treatment (UL+RL+SIM) at a dose of 10 mg/kg/d. All rats were sacrificed 6 weeks later, and the left femur was used for examination of bone mineral density, left tibia was used for bone histomorphometry analysis, the right femur and tibia were harvested for biomechanical test, and expression levels of type I collagen by real-time PCR and Western blot, respectively. Results 1. BMD of the CL group was significantly higher than those of the other three groups (P<0.05), and was markedly lower than those in the UL+RL and UL+RL+SIM groups (P<0.05). 2. The bone histomorphometry showed that BV/TV in the CL group was significantly higher than those in the other 3 groups, and the UL+RL and UL+RL+SIM groups showed a significantly higher BV/TV than that of UL group (P<0.05). The Tb.Th was significantly higher in the CL group than in the UL group. The Tb.Sp in the CL group was significantly lower than those in the other 3 groups (P<0.05). The UL+RL and UL+RL+SIM groups showed significantly lower Tb.Sp than that of the UL group (P<0.05). 3. Biomechanical test showed that the maximal load and elastic modulus in the CL groups were significantly higher than those of the other three groups (P<0.05). 4. Real-time PCR showed that no significant difference in the mRNA expression level of Col I was found between any two groups. 5. Western blot showed that the IOD of Col I is significantly lower than that in the CL group. Conclusions Bone loss, destruction of trabecular bone micro-architecture and biomechanical properties and reduction of type 1 collagen are present in tail-suspension treated rats, which are partially restored after reloading, and this recovery process is not enhanced by simvastatin treatment.