There are two categories of cells in the central nervous system; neurons and adjacent glial cells including astrocytes, microglia and oligodendrocytes. Accumulating evidence suggests that astrocytes actively participate in synaptic plasticity. On the other hand, long-term exposure to drugs of abuse could induce neuronal plasticity. Astrocytes undergo a process of prolifiration, morphological change, and enhancement of glial fibrillary acidic protein expression, termed activation of astrocytes. Recently, we demonstrated a dramatic increase in reactive astrocytes in the dorsal horn of the spinal cord following repeated in vivo treatment with morphine. We also found that in vivo treatment with morphine, which was associated with the rewarding effect, caused a robust astrocytic activation in the cingulate cortex. These data suggest that astrocytes may contribute to the synaptic plasticity induced by morphine during the development of dependence and tolerance. Therefore, this review focuses on several aspects of astrocytic response and discusses possible roles of astrocytes in the development of dependence and tolerance induced by morphine. We also report here that protein kinase C, Janus kinase/signal transducer and activator of transcription pathway, cyclin-dependent kinase 5 and tyrosine kinase cascade are directly involved in the neuron-glia communication during the development of synaptic plasticity induced by chronic morphine treatment.