ABSTRACT Objectives Glia (i.e., astrocyte and microglia) activation in the central nervous system plays a critical role in developing neuropathic pain. Microglia can be activated into pro-inflammatory(M1) or anti-inflammatory(M2) phenotypes. Switching microglial polarization from M1 to M2 phenotypes represents a novel therapeutic strategy for neuropathic pain. Curcumin has been widely used for its anti-inflammatory and immunomodulatory effects. This study investigated effects of curcumin on astrocyte activation and microglia polarization in the cuneate nucleus(CN), and development of neuropathic pain behavior after chronic constriction injury(CCI) of the median nerve. Methods Rats were fed with curcumin once daily at a dose of 40, 80 or 120 mg/kg 30 min before and until 7 days after median nerve CCI. Subsequently, mechanical allodynia and thermal hyperalgesia were evaluated using von Frey filaments and plantar tests, respectively. The levels of astrocyte marker GFAP, microglia marker Iba1, M1 maker CD86, and M2 maker CD206 in the CN were determined. ELISA were applied to measure cytokine concentrations. Results Curcumin administration dose-dependently reduced mechanical allodynia and thermal hyperalgesia, and decreased GFAP and Iba1 immunoreactivity in the ipsilateral CN after CCI. On ultrastructural observation, curcumin treatment was associated with fewer features of activated astrocytes and microglia. Furthermore, CCI rats given curcumin exhibited a decline in CD86 immunoreactivity and pro-inflammatory cytokine levels, but an increase in CD206 immunoreactivity and release of anti-inflammatory cytokines. Conclusions Our findings demonstrate that curcumin switches microglial phenotypes from M1 to M2 by suppressing astrocytic activation, reducing pro-inflammatory cytokine release and promoting anti-inflammatory cytokine production, and contributes to relief of neuropathic pain.