The goal of this study was to examine the ability of basic fibroblast growth factor (FGF-2) to promote reactivity and/or proliferation of astrocytes in vivo following brain injury, and the possible mechanisms involved. A small bilateral lesion in the motor-sensory cortex was performed, and either FGF-2, FGF-2 plus heparan sulfate, heparan sulfate, or saline was applied unilaterally in a piece of Gelfoam within the wound cavity. Following lesions, there was an increase in FGF-2 and FGF receptor (FGFR) immunoreactivities in the area surrounding the lesion in all the treatment groups. Rats that received treatment with recombinant FGF-2 alone showed an increase in the density of astrocytes as compared to the control group. The same group of rats exhibited an increase in the density of cells displaying FGF-2 immunoreactivity and cells displaying FGFR-1 immunoreactivity and cells displaying FGFR-1 immunoreactivity, and also an induction of FGF-2 mRNA in the tissue surrounding the lesion. The group of rats that received FGF-2 combined with heparan sulfate showed a larger increase in the same cellular parameters. Our results suggest that the FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by heparan sulfate. The action of FGF-2 on CNS injury appears to be part of an autocrine cascade that involves induction of FGF-2 and its receptor, thereby enhancing the ability of astrocytes to respond to FGF-2.