Neurodegenerative or autoimmune diseases are frequently regulated by chemokines and their receptors, controlling both glial activation and immune cell infiltration. CCL19 and CCL21 have been described to mediate crucial functions during CNS pathological states, regulating both immune cell traffic to the CNS and communication between glia and neurons. Here, we describe the expression pattern and cellular sources of CCR7, receptor of CCL19 and CCL21, in the normal mouse brain. Moreover, we found that CCR7 is upregulated in reactive astrocytes upon intracerebral LPS, regulating early glial reactivity through its ligands CCL19 and CCL21. Our results indicate that CCR7 is playing an important role for the intercellular communication during the inflammatory activation in the CNS.