It has been hypothesized that adipocytokines originating from adipose tissue may have an important role in bone metabolism. Vaspin is a novel adipocytokine isolated from visceral white adipose tissue, which has been reported to have anti-apoptotic effects in vascular endothelial cells. However, to the best of our knowledge there is no information regarding the effects of vaspin on osteoblast apoptosis. This study therefore examined the possible effects of vaspin on apoptosis in human osteoblasts (hOBs). Our study established that vaspin inhibits hOBs apoptosis induced by serum deprivation, as determined by ELISA and TUNEL assays. Western blot analysis revealed that vaspin upregulates the expression of Bcl-2 and downregulates that of Bax in a dose-dependent manner. Vaspin stimulated the phosphorylation of ERK, and pretreatment of hOBs with the ERK inhibitor PD98059 blocked the vaspin-induced activation of ERK, however, vaspin did not stimulate the phosphorylation of p38, JNK or Akt. Vaspin protects hOBs from serum deprivation-induced apoptosis, which may be mediated by activating the MAPK/ERK signaling pathway.