Objective To investigate the mechanism underlying ciliary neurotrophic factor (CNTF) involved in dedifferentiation of glial cells in injured optic nerves. Methods Sixty-five adult male SD rats were randomly divided into 3 groups: normal control group, optic nerve injured group and CNTF treat group. Optic nerves were harvested at the 7th or the 14th day after surgery and detected by gene chip, real-time PCR, HE staining and immunohistochemistry. Results Comparison with those of injury group, there were 608 genes expression up-regulated and 417 ones downregulated in the CNTF　treated group at the 7th day after operation, including genes related to chromatin configuration, transcription regulation, neural stem cells, neural differentiation and development, proliferation, apoptosis, ion channel, receptor, signal transduction and so on. Result of real-time PCR for selected genes was consistent with that of gene chip, supporting the validity of gene chip data. We also found that cells revealed by HE staining and immunoreactivity of Nestin, myelin basic protein (MBP), Erk1/2, and glial fibrillary acidic protein (GFAP) were increased in the distal optic nerves, but immunoreactivity of neurofilament (NF) was increased in the proximal optic nerves in the CNTF-treated group compared with the optic nerve injured group. Conclusion CNTF induces dedifferentiation of glia cells in the injured optic nerves and promotes regeneration of injured optic nerves through regulating the expression of related genes and proteins.