Our novel closed head injury model designated "Photo injury", which is created by exposing intense light to cortical tissue through thinned-skull cranial window, shows substantial cortical recovery (Suzuki et al, 2012). The recovering region is characterized by the prominent accumulation of perilisional nestin-expressing reactive astrocyte. In order to address the roles of the perilesional reactive astrocyte in wound healing, STAT3, which is crucial for astrocyte activation, has been ablated in nestin-expressing cells by using Nestin-Cre/STAT3^flox/flox mouse. Mice after more than seven days post-injury showed significantly less accumulation of perilesional reactive astrocytes, and larger lesion size in the STAT3-ablated group than in wild type group. The importance of STAT3 signaling was further confirmed by ablating SOCS3, which suppress cytokine mediated STAT3 activation, in the nestin-expressing reactive astrocyte by using Nestin-Cre/SOCS3^flox/flox mouse. The SOCS3-ablated groups showed significantly smaller lesion size after more than seven days post-injury, as well as significantly larger region covered by perilesional reactive astrocyte, than corresponding wild type group. Our results indicates that cytokine-mediated STAT3 activation in perilesionl astrocytes leads to the accumulation of nestin-expressing reactive astrocyte, and then promote wound healing following closed-head injury.