Glucocorticoids are the leading cause of secondaryosteoporosis. In the current study, the in vivoeffects of Antarctic krill (Euphausia superba) oil (AKO) ondexamethasone-treated mice were investigated. Resultsshowed that AKO significantly prevents bone loss, asevidenced by improved bone mineral density, biomechanicalstrength, and cancellous bone microstructure. Fluorescencedouble-labeling of femur showed that AKOinduces new bone formation. Toluidine blue staining ofmarrow cavity indicated that AKO increases the number oftrabecula, and decreases the generation of adipose cells. Runt-related transcription factor 2 (Runx2) and Peroxisomeproliferator-activated receptor c (PPARc) are the switchesfor osteogenic and adipogenic differentiation of bonemarrow mesenchymal stem cells, respectively. AKO significantlypromoted the expression of Runx2 protein, andreduced PPARc expression in bone tissue. Furthermore,AKO increased the mRNA expression of osteogenesis-relatedgenes and decreased the expression of adipogenesisrelatedgenes. In conclusion, AKO improved glucocorticoid-induced osteoporosis via promoting bone formation.