Abstract: Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) of a GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated.Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by MTT assay. Real-time PCR was done to evaluate the apoptotic gene expression, osteogenic gene expression and ALP activity were also measured. Western blotting was performed to evaluate the MAPK proteins. Glucocorticoid-induced osteoporosis animal model was used for in vivo study.Results: and conclusion: MTT assay revealed that KRG prevents a loss of cell viability against dexamethasone (Dex) induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction (PCR) data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and BMPs as well as increased ALP activity in MC3T3-E1 cells compared to cells only treate with Dex. In addition, KRG increased AKT phosphorylation and decreased JNK phosphorylation. Also, Micro-CT analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.