Introduction: Estrogen plays an important role in the osteogenic differentiation of mesenchymal stem cells while stem cells from apical papilla (SCAPs) can contribute to the formation of dentin/bone-like tissues.To date, the effects of estrogen on the differentiation of SCAPs remain unclear.Methods: SCAPs were isolated and treated with 10-7 M 17beta-estradiol (E2).Their odonto/osteogenic potency and the involvement of mitogen-activated protein kinase (MAPK) signaling pathway were subsequently investigated by using methyl-thiazolyl-tetrazolium (MTT) assay, etc.Results: MTT and flow cytometry results demonstrated that E2 treatment had no effect on the proliferation of SCAPs in vitro, while alkaline phosphatase (ALP) assay and alizarin red staining showed that E2 could significantly promotes ALP activity and mineralization ability in SCAPs.Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot assay revealed that the odonto/ osteogenic markers (ALP, DMP1/DMP1, DSPP/DSP, RUNX2/RUNX2, OSX/OSX and OCN/OCN) were significantly up-regulated in E2-treated SCAPs.In addition, the expression of phosphor-p38 and phosphor JNK in these stem cells was enhanced by E2 treatment, so was the expression of the nuclear downstream transcription factors including phosphor-Sp1, phosphor-Elk-1, phosphor-c-Jun and phosphor-c-Fos, indicating the activation of MAPK signaling pathway during the odonto/osteogenicdifferentiation of E2-treated SCAPs.Conversely, the differentiation of E2-treated SCAPs was inhibited in the presence of MAPK specific inhibitors.Conclusions: 10-7 M 17beta-estradiol enhanced the odonto/osteogenic differentiation of SCAPs via the activation of MAPK signaling pathway.