Astrocyte activation is involved in the neuropathic pain. As a glutamate scavenger, the glutamate transporter-1 (GLT-1) is exclusively expressed on the astrocytes and probably correlates with astrocyte activation. In the present study, we attempted to clarify the temporal changing courses of astrocyte activation and GLT-1 expression, as well as their correlations induced by a neuropathic pain model, namely, spinal nerve ligation (SNL) in which rapidly appearing (<3 days) and persistent (>21 days) mechanical allodynia and thermal hyperalgesia were presented. Immunofluorescent staining showed that GLT-1 was expressed exclusively in most (not all) of the astrocytes, even when the GLT-1 expression reached its peak. The expression of GLT-1 displayed an interesting biphasic change, with an initial up-regulation followed by a down-regulation after SNL. Our results also demonstrated that SNL induced a marked and long-term (>21 days) activation of astrocytes in the ipsilateral spinal dorsal horn. These results suggest that astrocyte activation, the change of GLT-1 expression and the potential relationship between them might play key roles in the induction and/or maintenance of neuropathic pain. The present results provide novel clues in understanding the mechanisms underlying the involvement of astrocytes and GLT-1 in the neuropathic pain. Anat Rec, 291:513–518, 2008. © 2008 Wiley-Liss, Inc.