OBJECTIVE： To study the improvement effects of Zhuanggu shenjin capsules （ZGSJC） on prednisone-induced osteoporosis model rats and its mechanism. METHODS： 72 SD rats were randomly divided into 6 groups as blank control group （normal saline）， model group （normal saline）， Gushukang granule group [positive drug， 3 g（crude drug）/kg] and ZGSJC low-dose， medium-dose and high-dose groups [1.4， 2.7， 5.4 g （crude drug）/kg]. Except for intragastric administration of normal saline in blank control group， other groups were given Prednisone acetate tablet 4.5 mg/kg intragastricallly every Monday and Thursday to induce osteoporosis model， and given relevant medicine intragastrically from Monday to Saturday for consecutive 13 weeks. Bone density （BMD）， bone histomorphometry indicators [volume percentage of bone trabecula， mineralization rate of bone trabecular （MAR） and mineralization rate of bone cortical （mAR）] and the expression of muscle segment homeebox gene Msx-2 mRNA and protein were all determined. RESULTS： Compared with blank control group， BMD， volume percentage of bone trabecula and the expression of Msx-2 mRNA and protein in renal tissue decreased， while mAR increased in model group （P＜0.05 or P＜0.01）. Compared with model group， volume percentage of bone trabecula and the expression of Msx-2 mRNA in renal tissue increased in Gushukang granule group and ZGSJC high-dose group， while mAR decreased； BMD and the expression of Msx-2 protein increased in treatment groups， as well as the volume percentage of bone trabecula increased in ZGSJC medium-dose group， with statistical significance （P＜0.05 or P＜0.01）， while the difference of MAR without statistic significance （P＞0.05）. CONCLUSIONS： ZGSJC can protect rats against prednisone-induced osteoporosis， and its mechanism may be associated with the up-regulation of Msx-2 expression in renal tissue.