Abstract: The aim of the present study was to investigate the effects and possible mechanisms of baicalin on morphine induced microglia activation and morphine tolerance. Cytokine IL-1β and TNF-α expression were analyzed by reverse transcription polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA), and the level of p38 MAP kinase phosphorylation and IBA-1 expression was determined by Western blot, the antinociception and morphine tolerance were assessed in mice using hot-plate test. Results showed that baicalin(1, 10, 100 μmol/L)inhibited morphine induced up-regulated levels of IL-1β, TNF-α in BV-2 microglia cells in a dose-dependent manner; and that 100 μmol/L baicalin significantly inhibited the level of p38MAP kinase phosphorylation induced by morphine in BV2 microglia cells. Intrathecal(it. )injection of baicalin(20, 40, 60 μg)attenuated the development of chronic morphine tolerance in a dose-dependent manner. Baicalin(60 μg)mimicked the role of minocycline and significantly suppressed the level of p38MAP kinase phosphorylation induced bychronic morphine treatment and IBA-1expression in mice spinal cord. In conclusion, baicalin suppresses morphine-induced microglia activation through suppressing p38MAPK signaling, resulting in significant attenuation of morphine antinociceptive tolerance.