Background Signal transducers and activators of transcription 3(STAT3) is one of the seven members of the STATs family and mediates a wide variety of biological functions in the central and peripheral nervous systems. Objective To provide a review about the role and the possible mechanisms of STAT3 in neuronal development and regeneration. Content STAT3 is activated in response to the multiple cytokines, free radicals and other inflammatory mediator that are produced in damaged neural tissue. Activated STAT3 translocates to the nucleus, binds to the specific promoters of target genes, and induces gene expression, leads to neuroprotection. Trend Defining the endogenous molecular mechanisms that lead to neuroprotection by STAT3 after injury might identify novel therapeutic targets against neural tissue ischemic damage and neuropathic pain.