Murine microglia N9 cells were activated by both the water extract of Rhizoma coptidis (WEC) and berberine by the regulation of mitochondrial Δψ, free radicals, as well as three genes of Ndufab1, Cox6a2 and Atp5a1. However, WEC induced this activation more remarkably than berberine, which ascribed to its specific modulation of Atp5c1 gene expression and Ca 2+ influx.