Adenosine is a nucleoside widely distributed in the organism with neuromodulative and neuroprotective activity in CNS. In a recent in vivo study, short-term administration of adenosine was shown to promote remyelination while modulated the expression of inflammatory cytokines in mice with cuprizone-induced demyelination. The aim of this study was to examine if adenosine effects on microglia activation and influences the dynamic conversions of activated microglia. For this purpose, microglia were isolated from the brain of newborn mice and cultured in the presence of lipopolysaccharide(LPS, a pro-inflammatory mediator) at various concentrations. LPS, at the concentration of 100 ng/ml, was found to stimulate the proliferation of microglia and increase levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in the culture medium. And the treatment increased the number of iNOS positive cells, indicating the conversion of resting microglia to M1 microglia. In a subsequent experiment, adenosine at various concentrations was added into the culture medium of primary microglia pre-treated with LPS(100 ng/ml). Twenty-four hrs later, the levels of IL-1β, IL-6, TNF-α, IL-10, IGF-1, and TGF-β in the medium were measured. The LPS-induced increases in IL-1β, IL-6, and TNF-α were dose-dependently attenuated or reversed by adenosine, while levels of IL-10 and IGF-1 increased. In the meanwhile, adenosine increased the numbers of iNOS positive and CD206 positive cells, and elevated the expression of iNOS and Arg1 in the LPS pretreated microglia, although it showed no effect in the absence of LPS. These data for the first time provide evidence that adenosine may change the phenotype conversion of activated microglai from M1 to M2.