Aims: Depressive symptoms in children and adolescents are commonly treated with serotonin re-uptake inhibitors like fluoxetine. Astrocytes expressing different serotonin receptors (5-HTRs) and the serotonin transporter (5-HTT) are affected by fluoxetine administration. The study was conducted to revise whether fluoxetine treatment during postnatal brain development results in long-term changes of astroglia. Methodology: Thus, immunohistochemistry and real-time PCR analyses were performed at different postnatal periods in rats to investigate short- and long-term changes following by a 14-day administration with fluoxetine (5 mg/kg/BW s.c. once daily). Results: Fluoxetine-treatments from postnatal day (pd) 1-15, measured at pd 16, led to a significant reduction of GFAP gene (Gfap) in hippocampus and GFAP protein expression in the dentate gyrus and CA1 without changes at pd 90 compared to controls. Treatments from pd 21-35 resulted in a significant decrease of Gfap and protein (measured 24 hours after last injection) in striatum (putamen), frontal cortex and hippocampus. Contrary, if measured at day 90, the same treatment led to a significant increase in those regions. Later treatments from pd 50-64 did not result in significant changes in mRNA or in protein expression. Conclusion: This study revealed a fluoxetine-sensitive period of brain astrocyte development (i.e. periadolescence) that led to structural effects, which can even be detected in adulthood. These results might be relevant for psychopharmacological treatment in children and require continuative clinical studies.