The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and infl ammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinfl ammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic infl ammation and produced defi cits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration signifi cantly decreased expression of pro-infl ammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these fi ndings suggest that GRg3 signifi cantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-infl ammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer`s disease, by improving cognitive and memory functions due to its anti-infl ammatory activity in the brain.