We investigated the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) in stab and freeze brain injury models in rats. Immunohistochemical staining with anti-VEGF antibodies demonstrated an increase in VEGF-positive cells in and around both lesions. Morphologically, the injury-induced VEGF-positive cells resembled astrocytes. Double immunofluorescent staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and VEGF demonstrated directly that VEGF-positive cells which appeared in response to these injuries were astrocytes. VEGF expression in astrocytes was maximal on days 3 and 4 after injury in terms of both cell number and affected area. The increase in VEGF-positive cells was more widespread in the freeze lesion than in the stab wound, and occurred in both the lesioned and nonlesioned hemispheres. VEGF-positive cells were still present 3 weeks after both injuries, but their numbers were reduced and their distribution became limited to the immediate vicinity of the lesions. These observations indicate that astrocytes react to injury by increasing VEGF expression, suggesting that VEGF might participate in the central nervous system response to injury.