Background: Glucagon-like peptide-2 (GLP-2) is an intestinal trophic factor that induces astrocyte proliferation through its own receptor (GLP-2R), but the control of its expression is not well known. Objective: To study the effects of glucose and of different mitogenic agents on the control of GLP-2R expression in cultured rat astrocytes. Methods: GLP-2R mRNA content was measured by quantitative RT-PCR. Results: GLP-2R expression was higher in proliferating than in resting cells. The expression was dependent of glucose concentration both in the absence and in the presence of GLP-2. In the presence of a high glucose concentration, GLP-2, PDGF, and PDGF plus GLP-2 presented opposite effects depending on the incubation time. However, insulin, IGF-1, and EGF alone, and plus GLP-2 had no effect. IGF-2, but not IGF-2 plus GLP-2, increased the expression. On the contrary, NGF decreased the GLP-2R expression, but NGF plus GLP-2 increased it even until values similar to those obtained with GLP-2 alone. Interestingly, in the presence of a low glucose concentration, leptin and NPY produced a significant reduction of GLP-2R expression. Conclusion: Astrocytes are distributed throughout the brain, where GLP-2 appears to have important functions. Since these cells express the GLP-2R, the results of this study could be considered of interest to advance the knowledge of the role of GLP-2 signaling in the CNS, which should lead a better understanding of the events that occur under normal and pathophysiological conditions.