Abstract: 【Abstract】 Objective To investigate whether minocycline could inhibit neuroinflammation induced by microglia activation through suppression of adenosine A_2Areceptor _(A2AR)expression in rats after cerebral ischemia/reperfusion (I/R) injury. Methods Thirty male Sprageue-Dawley rats were randomly divided into 3 groups: sham group, I/R group and minocycline group. The rats were subjected to occlusion of the right middle cerebral artery (MCAO) for 2 h to establish stroke I/R model, and 3 mg/kg minocycline was injected intravenously immediately after reperfusion twice a day in minocycline group. At 24 h after I/R, the inflammatory cytokines IL-1β and IL-6 in peri-infarct region were measured by Western blot, microglia activation was detected by double-immunofluorescence labeling. A_2AR density was detected by immunohistofluorescence and Western blot. Results The number of CD11b-positive cells in I/R group was increased when compared with that in sham group. The expressions of IL-1β, IL-6 and A_2AR were markedly up-regulated after I/R. Minocycline significantly decreased the expressions of IL-1β, IL-6 and A_2AR and the number of CD11b-positive cells in peri-infarct region. Conclusion Minocycline could prevent cerebral ischemia induced neuroinflammation by the suppression of microglial activation, which may be related to down-regulation of A_2ARexpression.