Objective To evaluate the efficacy of isoflavone (IS)-loaded mesoporous glass cement scaffold materials in repairing the rabbit femoral bone defect. Methods Various composite glass cements absorbing plant hormones (soy isoflavone) were fabricated as follows: calcium sulphate (CS), 20% mesoporous magnesium calcium silicate/calcium sulfate (20 m-MCS/CS), and 40% mesoporous magnesium calcium silicate/calcium sulfate (40 m-MCS/CS). The in vitro isoflavone release profiles of the above materials were evaluated. Sixty New Zealand rabbits were randomized into 4 groups with 15 in each group, and the bone defect models in the distal end of femur were created. Group A: implanted with CS; Group B: 20 m-MCS/CS; Group C: 40 m-MCS/CS; and Group D: IS-loaded 40 m-MCS/CS (40 m-MCS/CS/IS). The rabbits were sacrificed at 4 weeks, 8 weeks and 12 weeks postoperatively and the bone samples were scanned with micro-CT. Then histology analysis was conducted under microscope after decalcification and Masson trichrome staining. Results Controlled release profiles of isoflavone were presented in both 20 m-MCS/CS/IS and 40 m-MCS/CS/IS groups, and a higher cumulative release rate was detected in 40 m-MCS/CS/IS group, which reached (41.0±1.8)% on the 25^th day; therefore 40 m-MCS/CS/IS was selected for further evaluation in vivo, and 40 m-MCS/CS, 20 m-MCS/CS and CS served as controls. Rabbits in Group A implanted with CS showed little new bone formation 12 weeks after operation; those in Group B implanted with 20 m-MCS/CS presented with better bone regeneration in the defect site; and the bone defect sites in group C grafted with 40 m-MCS/CS were almost filled with neo-bone; however, the best results were obtained in group D which was implanted with 40 m-MCS/CS/IS, with the defects fully repaired by the bone trabecular. Conclusion Isoflavone-loaded mesoporous glass cement can effectively repair lacunar bone defects, and may serve as a promising new bone regeneration material.