Although glucocorticoids provide benefits for inflammation or autoimmune disorders, high-dose and long-term use could cause osteonecrosis or osteoporosis as adverse effect for patients. Electromagnetic field (EMF) treatments have been clinically used for many years to promote fracture healing, but whether EMF can attenuate the deleterious effects of glucocorticoids is not clear. In this study, the effects of different concentrations of dexamethasone (DEX) on proliferation and adipogenic or osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were detected and compared, and the effects of EMF treatment (15Hz, 1mT, 4h/day) on 0.1 mu M DEX-modulated BMSCs' proliferation and adipogenic or osteogenic differentiation were investigated. Higher concentrations of DEX (0.1 and 1 mu M) inhibited proliferation of BMSCs but promoted expression of adipogenic-related genes, increasing the number of lipid droplets. In the early stage of differentiation, DEX restrained expression of RUNX2 and alkaline phosphatase (ALP), but amplified expression of ALP and osteopontin (OPN) in the late stage. EMF treatment of BMSCs influenced by 0.1 mu M DEX inhibited the high expression of adipogenic-related genes, stimulated the expression of RUNX2, ALP, OPN, and osteocalcin, and increased the activity of ALP. EMF exposure augmented the expression of p-ERK, which DEX reduced. After using mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway inhibitor, U0126, the effect of EMF was reduced. In conclusion, EMF exposure accelerates BMSCs proliferation, inhibits adipogenic differentiation, and promotes osteogenic differentiation of BMSCs modulated by DEX, and these effects are mediated at least in part by MEK/ERK signaling pathway. Bioelectromagnetics. 35:479-490, 2014. (c) 2014 Wiley Periodicals, Inc.