Oligodendrocytes (OLs) are glial cells that form myelin sheaths in the central nervous system. Myelin sheath plays important role in nervous system and loss of it in neurodegenerative diseases can lead to impairment of movement. Understanding the signals and factors that regulate OL differentiation can help to address novel strategies for improving myelin repair in neurodegenerative diseases. The aim of this study was to investigate the role of insulin-like growth factor-binding proteins 7 (IGFBP-7) in differentiating OL precursor cells (OPCs). It was found that oligodendrocyte precursors undergoing differentiation were accompanied by selective expression of IGFBP-7. In addition, knockdown of IGFBP-7 promoted differentiation of oligodendrocytes and increased formation of myelin in cultured cells. In contrast, excessive expression of IGFBP-7 inhibited differentiation of oligodendrocytes. Furthermore, overexpression of IGFBP-7 in oligodendrocyte precursor cells increased transcription of Wnt target genes and promoted -Catenin nuclear translocation. These findings suggest that IGFBP-7 negatively regulates differentiation of oligodendrocyte precursor cells via regulation of Wnt/-Catenin signaling. Overexpression of IGFBP-7 in oligodendrocyte precursor cells increased transcription of Wnt target genes and promoted -Catenin nuclear translocation. IGFBP-7 negatively regulates differentiation of oligodendrocyte precursor cells via regulation of Wnt/-Catenin signaling.