Methylmercury is an environmental pollutant that causes central nervous system injury. We reported that the expression of the inflammatory cytokines TNF-α and IL-1β was specifically induced in the brains of methylmercury-treated mice. In addition, we recently found that cytotoxic microglia (M1-microglia) may be involved in the induction of inflammatory cytokine expression by methylmercury in mouse cerebral slice cultures. In the current study, we investigated the involvement of M1-microglia in the neuronal cell death caused by methylmercury using mouse cerebral slice cultures. The results revealed that methylmercury activated steady state microglia (M0-microglia) to M1-microglia, but this activation was suppressed by pretreatment with minocycline, a microglial activation inhibitor. In addition, under the same conditions, minocycline suppressed neuronal cell death by methylmercury. These results suggest that methylmercury may induce neuronal cell death via activation to M1-microglia.