Objective Microglia are the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes, a critical component in several neurodegenerative diseases.Alcohol abuse has been considered as one of the commonly substrates of neurodegeneration although the causative factors are poorly understood.Here, we investigated whether activated microglia was implicated in neurodegeneration and cognitive dysfunctions in adult rats after long-term alcohol abuse.Methods Rats were given orally a priming dose of 5 g/kg ethanol and 3 g/kg additionally every 8 h for 4 consecutive days, followed by a 3-day ethanol-withdrawal period, which was repeated four times to simulate the binge drinking of human alcoholics.Microglia activation and neuronal death in brain were detected by immunohistochemistry and Fluoro-Jade B staining, respectively, on days 0, 4, 7 and 14 post-ethanol treatments.While, learning and memory abilities were assessed by novel object recognition and Y maze test on days 4, 7 and 14.Results The results showed that microglia activation was obvious in the cortex and hippocampus, which accompanied by neuronal death.Moreover, learning and memory abilities were also declined on day 4 post-ethanol treatment.However, the hypertrophied microglia disappeared and the ramified microglia proliferation was observed on day 4 up to 14 after the abstinence from ethanol, along with the gradual recovery of neuronal damage and cognitive impairment.Conclusion Thus the present study indicated that activated microglia are involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia likely contribute to the recovery during abstinence.