Abstract: Morphine is the most common potent analgesic for the treatment of severe pain. However, chronic administration of morphine would lead to the development of analgesic tolerance, and tolerance seriously inhibits the application of morphine in clinical medicine. To date, most studies on morphine tolerance have focused mainly on brain neurons. Recently, compelling evidences show that glia cells, especially microglia and astrocyte, also play a pivotal role. The article reviews the advances in the role of glia cells in the potential mechanisms and efficient treatments to morphine tolerance.