Abstract: Objective To establish a rat model of postmenopausal osteoporosis(PMOP)and explore role of resveratrol(RES)in promoting cell proliferation of rats with PMOP. Methods Totally 80 clean SD rats were randomly divided into control group, PMOP group, low dose RES group(60 mg/kg), medium dose RES group(80 mg/kg)and high dose RES group(100 mg/kg), with 16 rats in each group. Rats were treated with bilateral ovariectomy and RES as preventive treatment one week after operation, and body weight was measured every month. After 24 weeks, blood samples were collected from the heart after sacrifice and bilateral femurs were taken. Bone mineral density was measured by bone densitometer, levels of p53 and Cyclin-D1 were detected by reverse transcription polymerase chain reaction(RT-PCR), and the expression of Notch-1 protein was detected by Western blot. Results The bone mineral densities of femur and vertebrae in the PMOP group decreased significantly, and bone mineral densities of femur and vertebrae in the groups with different RES concentrations were significantly higher than those in the PMOP group(P<0.05). Compared with the control group, the mRNA transcription levels of p53 and Cyclin-D1 in the PMOP group were significantly higher, and the mRNA transcription levels of Cyclin-D1 in the groups with different RES concentrations were significantly higher than that in the PMOP group, while the mRNA transcription level of p53 was significantly lower(P<0.05). Western blot results showed that the expression level of Notch-1 in the PMOP group was significantly inhibited, and the expression level of Notch-1 in the groups with different RES concentrations was significantly higher than that in the PMOP group(P<0.05). Conclusion RES plays a role of antagonizing osteoporosis through regulating Notch-1 signaling pathway for promotion of cell proliferation in bone tissue.