Magnesium (Mg) alloys, having a unique combination of strength and degradation, are being explored for various craniofacial and orthopedic applications. Nevertheless, the underlying mechanism of Mg2+ to stimulate bone formation needs further investigation. In this in vitro study, the degradation behavior of pure Mg and the effect of Mg2+ on the activity of osteoblasts were elucidated. From the corrosion test, it was determined that the degradation of pure Mg was able to create an alkaline microenvironment. It was further determined that Mg2+ promoted the proliferation and differentiation of osteoblasts. By western blotting analysis, it was noted that Mg2+ increased the phosphorylation of ERK (enhanced the c-fos level) and induced GSK3β phosphorylation (enhanced the β-catenin levels). These results demonstrated that the degradation of Mg was able to promote the proliferation and differentiation of osteoblasts, which may be related to the newly created alkaline microenvironment and the osteogenesis potential of released Mg2+ through the MAPK/ERK signaling pathway.