Cross-talks between microglia and astroglia is of key importance in the pathogenesis of several neurological disorders. Upon nervous injury, microglia become activated and release mediators which influence neighbour neuronal and astroglial cells. In particular, astroglial cells are thought to adapt the expression of proteins involved in glutamate handling, a process that could putatively participate in the development or progression of excitotoxic insults. We herein hypothesized that soluble mediators released by activated microglia induce changes in the expression of astroglial metabotropic glutamate receptors (mGluRs), which we previously showed to be implicated in the control of glutamate transmission by astrocytes. In this aim, an in vitro model was designed where microglial cells cultivated from neonatal rat cerebral cortex were activated with lipopolysaccharide. After 48 hours, real-time quantitative PCR (q-PCR) were performed to validate the activation state of microglia. In parallel, the conditioned media from these cells were transferred to primary cultures of astrocytes which were then examined after 72 hours. Quantitative PCR were realized on these astroglial cultures to evaluate the effects of this inflammatory environment on the expression of mGluR3 and mGluR5, the two principal subtypes identified on glial cells. We evidenced a robust microglial activation by lipopolysaccharide as shown by increases in transcripts of the pro-inflammatory enzymes iNOS and COX-2, and the cytokines TNFa, IL-1b, or IL-6. The conditioned medium collected from activated microglia was found to induce an opposite regulation of the glutamate receptors on astrocytes, as mGluR3 was upregulated while mGluR5 was downregulated. We conclude that activated microglia release diffusible factors which differentially affect the astroglial expression of mGluR 3 and 5. Because these receptors are thought to contribute to the control of glutamate handling and since these receptors activate distinct signaling cascades, our future objective is to understand the molecular mechanisms supporting these regulations and to investigate the impact on excitotoxic events which affect neurological disorders.