OBJECTIVE To investigate the effect of Chinese herb medicine compound on bone lose in rats under 3 weeks simulated weightlessness, and to observe the synergistic action of other ingredients in the compound on calcium. METHODS Thirty male Wistar rats were divided into 3 groups: control group, tail-suspend group, tail-suspend and medicine group which took Chinese herb medicine compound (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by gastric administration. After 3 weeks simulated weightlessness, serum calcium (Ca), phosphorus (P), bone mineral density (BMD) and content (BMC), bone mechanical properties (MEC) were observed. RESULTS At the end of the experiment, serum Ca and P increased significantly (P<0.01), BMD and BMC of posterior body decreased significantly (P< 0.01) in tail suspend rats, compared with in the control group. In rats of tail suspended and medicine group, the increase degree of serum Ca and P were smaller, BMD and BMC of posterior body increased significantly (P<0.01 or 0.05), and MEC also tend to increase. CONCLUSIONS Bone mass of posterior body lose significantly, with mechanical property significantly decrease in rats after 3 weeks simulated weightlessness. Chinese herb medicine compound is effective to prevent the change of bone. Simple calcium supplement can not prevent simulated weightlessness induced bone loss, therefore other ingredients in the compound may perform synergistic action to calcium (Concha Ostreae prepared by acetic acid).