Abstract: OBJECTIVE To investigate the effects of ferulic acid (FA) on osteoblast apoptosis and its mechanism， and explore the potential therapeutic effects of FA on osteoporosis. METHEODS The pre-osteoblast cell line MC3T3-E1 was selected. The effect of FA on cell viability was observed by MTT assay. Apoptosis was detected by flow cytometry. The expression of apoptosis-related protein Bcl-2 was detected by Western blot. Flow cytometry and DCFH-DA fluorescence staining were performed to observe the reactive oxygen species (ROS) level. The nuclear localization of FoxO3a， one member in the forkhead box (Fox) family， was observed by immunofluorescence. The G protein coupled receptor 30 (GPR30) specific antagonist G15 was used to observe FA effect. RESULTS FA showed no significant effect on normal cells in the dose range of 25~400 μmol/L， but promoted the cell viability after hydrogen peroxide injury. Flow results showed that FA could reduce cell apoptosis rate and ROS level after peroxidation injury. Immunofluorescence results indicated that FA could inhibit the apoptosis and the nuclear content of oxidative stress-related protein FoxO3a under peroxidative conditions. After treatment with G15， the effects of FA on decreasing apoptosis， lowering ROS levels， and reducing the content of FoxO3a in the nucleus were significantly blocked. CONCLUSION FA shows the ability to resist osteoblast apoptosis， reduce intracellular ROS levels， and prevent FoxO3a nuclear translocation under conditions of peroxidative damage. The mechanism may be related to the membrane estrogen receptor GPR30.