Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI.