Objective To investigate the effects of simvastatin on the bone loss and deterioration of bone quality with different intervention programs. Methods Thirty two 3-month-old female Sprague-Dawley (SD) rats were randomized into 4 groups of 8 animals in each: All rats but those in the sham group (A) received bilateral ovariectomy, and treated by vehicle (B), simvastatin (5 mg/kg/day) at first half period (C) or at latter half period (D). The rats in group C received simvastatin by a gavage after the OVX operation immediately, and stopped at 10 weeks after OVX. The rats in group D began to receive simvastatin treatment from 10 weeks after OVX and ended at 20 weeks after OVX. At week 20, all rats were sacrificed and the concentrations of serum PINP and ICTP were detected by ELISA, L3 vertabra was used to detect the bone mineral density, L4 vertebra was used to analyze the maximum loading and elastic modulus by compression test, and the microstructure of the L5 vertebra was detected by micro-computed tomography. Results 1. ELISA analysis: the concentrations of serum P1NP and ICTP in the groups A, B and C were significantly higher than that of group A (P<0.05). 2. BMD test showed that the rats in group B had significantly lower BMD than the other 3 groups (P<0.05), while the BMD of groups C and D were markedly lower than that of group A (P<0.05). 3. Biomechanical test: the maximum load and elastic modulus of L4 vertebrae in the group B were significantly lower than the other 3 groups (P<0.05), and those of the groups C and D were markedly lower than that in the group A (P<0.05). 4. micro-CT: BV/TV and Tb.N in the sham operated rats were significantly higher than those of the other 3 groups, while the opposite trends was found in Tb.Sp (P<0.05), and the Tb.Sp in the groups C and D were significantly lower than that of group B (P<0.05). Conclusions Our data demonstrate that bone loss and deterioration of bone micro-structure and biomechanical properties occurred at 20 weeks after ovariectomy, both the first-half-period and latter-half-period treatment by simvastatin may partially prevent these changes, but can not restore the BMD to normal level.