${alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${alpha}$-Asarone significantly reduced TNF-${alpha}$ and IL-$1{eta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${alpha}$-asarone treatment. ${alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${alpha}$-asarone treatment. In the Morris water maze test, ${alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${alpha}$-asarone may be one of the mechanisms for the ${alpha}$-asarone-mediated ameliorating effect on memory deficits.