Abstract: Objective To study the curative effect of puerarin combined with zinc on osteoporosis in ovariectomized rats and discuss the function of drug combination against osteoporosis in ovariectomized rats. Methods Sixty female SD rats were randomly divided into 6 groups: sham operation group, control group, zinc supplementation group, puerarin group, estradiol group and combination therapy group. The rats received bilateral ovariectomy (the other 5 groups) or sham operation (SHAM group) respectively. The rats in the zinc supplementation group, the puerarin group, the estradiol group and the combination therapy group were given zinc supplementation, puerarin, estradiol Alcohol and puerarin combined with zinc supplementation, respectively. After 10 weeks of treatment, the changes of serum zinc, calcium, phosphorus, alkaline phosphatase (ALP), osteocalcin, CTX, OPG and RANKL; lumbar 4 and femoral bone mineral density (BMD); tibial bone micro-parameters were tested and analyzed. Results BMD of puerarin group, zinc supplementation group, estradiol group and combination therapy group were significantly increased. The mean values of BV/TV, Tb.Th, Tb.Sp, and serum levels of serum zinc, calcium, phosphorus, alkaline phosphatase (ALP), osteocalcin, CTX, OPG and RANKL were improved obviously when compared with the control group (all P<0.05). Compared with the puerarin group and zinc supplementation group, the above indexes in the combination therapy group were improved more obviously (all P<0.05). Conclusion The puerarin and zinc show synergistic effects on both stimulation of bone formation and suppression of bone resorption in ovariectomized rats, thereby increase bone mass.