The aim of this study was to investigate the immunogenicity of human umbilical cord mesenchymal stem cells (hUCMSCs) cultured in vitro by detecting changes in major histocompatibility complex expression. Major histocompatibility complex expression was detected by RT-PCR and flow cytometry. Morphologically, hUCMSCs exhibited no visible changes before the 5 st passage of the in vitro culture. In addition, At the molecular level, the cells continued expressing the specific positive surface markers, CD105, CD73 and CD90, and did not express the negative surface markers, CD14, CD34 or CD45, during culture ex vivo. Furthermore, the hUCMSCs exhibited low immunogenicity, which was maintained when cultured for five passages. Taken as a whole, these results suggested that hUCMSCs cultured in vitro may be safely for transplanted because of low immunogenicity before the fifth passage.