Bone development is a dynamic process involving the balance between osteoblasts formation and osteoblasts resorption. Lipopolysaccharide (LPS) can break this balance and cause bone injury. Cynomorium songaricum is a Chinese herb that could stimulate osteoblast proliferation and inhibit osteoclast formation. This study aimed to investigate the effects of CSE on the apoptosis and differentiation of osteoblast modulated by LPS. Osteoblastic MC3T3-E1 cell line was used as the experimental model and our results showed that CSE relieved LPS induced inhibition of MC3T3-E1 cell proliferation. Moreover, we found that alkaline phosphatase activity was markedly inhibited by LPS, but could be recovered by CSE. These data suggest that LPS inhibits osteoblast proliferation and differentiation, and CSE antagonizes these inhibitory effects of LPS on osteoblast proliferation and differentiation. Furthermore, we demonstrated that CSE inhibited LPS induced caspase-3 activity in MC3T3-E1 cells, and LPS induced upregulation of caspase-3 and Bax and downregulation of Bcl-2 in MC3T3-E1 cells. These data suggest that LPS induces osteoblast apoptosis while CSE protects osteoblast from LPS induced apoptosis. In conclusion, CSE promotes osteoblast differentiation and inhibits lipopolysaccharide induced apoptosis of osteoblast.