Objective To investigate the effect of mangiferin on postmenopausal osteoporosis and inflammation in rats. Methods Sixty female SD rats were randomly divided into control group, model group and mangiferin small (50 mg·kg ^-1), medium (100 mg·kg ^-1) and large (200 mg·kg ^-1) dose groups, with 12 rats in each group. The osteoporosis model was established in both the model group and the experimental group according to bilateral ovariectomy, while only the adipose tissue near the ovary was removed in the control group. The expressions of bone mineral density, bone microstructure, bone metabolism indexes, inflammatory factors and related proteins were observed in each group. Results Compared with the control group, bone mineral density, bone trabecular (TB) number and bone trabecular thickness of the model group were significantly decreased, bone trabecular separation was significantly increased, serum PINP, BGP, ALP levels were significantly decreased, TNF-α, IL-6, IL-8 levels were significantly increased, NF-κB, MMP9 mRNA expression levels were significantly increased (P<0.05). Compared with model group, BMD, bone trabecular number, bone trabecular thickness, PINP level, TNF-α and IL-8 levels, NF-κB and MMP9 mRNA levels in mangiferin low-dose, medium-dose and high-dose groups were significantly increased (P<0.05). The level of bone trabecular separation in mangiferin medium dose group and high dose group was significantly decreased, the level of BGP and ALP was significantly increased, and the level of IL-6 was significantly decreased (P<0.05). Conclusion Mangiferin has a good effect in postmenopausal osteoporosis rats, which may be related to the inhibition of inflammatory response and inflammatory signaling pathway (NF-κB/MMP9).