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Objective Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs), which are responsible for myelination.However, the molecular mechanisms of maturation and myelination by oligodendrocytes remain elusive.The present study is aim to explore the roles of SHP-2 in oligodendrocytes maturation.Methods In this study, we first searched the potential tyrosine phosphatases involved in oligodendrocytes maturation using OPCs as the model.Then, we characterized SHP-2 expression during the development of oligodendrocytes by RTPCR, immunostaining and Western blot.The roles of SHP-2 in olidendrocytes maturation were detected by gene manipulations subsequently.Finally, the mechanism was examined by detecting activities of concerned kinases.Results (1) We found that SHP-2 was persistently expressed during developmental process of oligodendrocytes.(2) SHP-2 knock down attenuated oligodendrocytes maturation and this effect was triiodo-L-thyronine (T3) dependent.Over-expression of SHP-2 promoted maturation in primary cultured oligodendrocytes.(3) It has been identified that SHP-2 may regulate oligodendrocytes maturation through Akt and Erk1/2 signaling.Conclusions SHP-2 promotes oligodendrocytes maturation via Akt and ERK1/2 signaling in vitro.