Objectives : Neuroinflammation is characterized by microglial activation and the expression of major inflammatory mediators. The present study investigated the inhibitory effect of ginsenoside Rg1 ($GRg_1$), a principle active ingredient in Panax ginseng, on pro-inflammatory cytokines and microglial activation induced by systemic lipopolysaccharide (LPS) treatment in the mouse brain tissue. Methods : Varying doses of $GRg_1$ was orally administered (10, 20, and 30 mg/kg) 1 h before the LPS injection (3 mg/kg, intraperitoneally). The mRNA expression of pro-inflammatory cytokines in the brain tissue was measured using the quantitative real-time PCR method at 4 h after the LPS injection, Microglial activation was evaluated using western blotting and immunohistochemistry against ionized calcium binding adaptor molecule 1 (Iba1) in the brain tissue. Cyclooxigenase-2 (COX-2) expressions also observed using western blotting and immunohistochemistry at 4 h after the LPS injection, In addition, double-immunofluorescent labeling of tumor necrosis factor-${alpha}$ (TNF-${alpha}$) and COX-2 with microglia and neurons was processed in the brain tissue. Results : $GRg_1$ (30 mg/kg) significantly attenuated the upregulation of TNF-${alpha}$, interleukin (IL)-$1{eta}$ and IL-6 mRNA in the brain tissue at 4 h after LPS injection. Morphological activation and Iba1 protein expression of microglia induced by systemic LPS injection were reduced by the $GRg_1$ (30 mg/kg) treatment. Upregulation of COX-2 protein expression in the brain tissue was also attenuated by the $GRg_1$ (30 mg/kg) treatment. Conclusion : The results suggest that $GRg_1$ is effective in the early stage of neuroinflammation which causes neurodegenerative diseases.