This study investigated the time course of the striatal lesions produced by continuous local injection of the glutamate uptake inhibitor, L‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) at the rate of 25 nmol/h in rats. The extent of the neurodegeneration area (defined as the lesion area) did not significantly vary with the duration of the PDC treatment between 3 and 14 days, but was markedly reduced 3 months after cessation of the 14‐day treatment, probably reflecting striatal atrophy. After the 3‐day treatment, the lesion zone showed calcium precipitates and marked microglial reaction contrasting with the reduction of astroglial labeling and loss of the glutamate transporter GLT1 mRNA expression; however reactive astrocytes were observed around the lesion. After the 14‐day treatment, the lesion zone presented reactive astrocytes and microglia without calcification, and a partial recovery of GLT1 mRNA expression. Interestingly, the growth arrest DNA damage‐inducible GADD45 mRNA expression was induced around the lesion after 3 days but inside the lesion after 14 days of treatment. Three months after the 14‐day treatment, the astroglial reactivity persisted within the lesion whereas most of the other markers examined tended to normalize. These data suggest that defective glutamate transport induces primary death of neurons and dysfunction of astrocytes. They strongly implicate reactive astrocytes with GLT1 and GADD45 transcripts in preventing secondary neuronal death. GLIA 29:222–232, 2000. © 2000 Wiley‐Liss, Inc.