ERS is a kind of universal existence in various cellular stress response.Recently, the research shows that ERS may affect bone metabolism balance from different ways.However, the specific mechanism is still not clear.The relationship between ERS and osteoporosis needs further research.This article will firstly introduce the pathways of ERS, then the relationship between the ERS and osteoporosis will be discussed from pancreatic beta cells, osteoblasts, osteoclasts and mesenchymal stem cells.Lastly, I will give perspectives on the future research on treatment of osteoporosis drug.