Objectives : Tetramethylpyrazine (TMP) is an active ingredient in Ligusticum wallichii and has a wide range of neuroprotection effects. This study investigated anti-neuroinflammatory effect of TMP on brain regions in intracerebroventricular (i.c.v.) lipopolysaccharide (LPS)-treated C57BL/6 mice, Methods : TMP was administered intraperitoneally at doses of 10, 20, and 30 mg/kg at 1 h prior to LPS (3 mg/kg) i.c.v. injection. mRNA level of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF- α), interleukin (IL)-1β and IL-6, was measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Cyclooxygenase-2 (COX-2) positive cells in the hypothalamus was also observed using immunohistochemistry at 24 h after the LPS injection, Results : At a dose of 30 mg/kg TMP significantly attenuated up-regulation of TNF-α and IL-1β mRNA in the cerebral cortex and IL-1β mRNA in the hippocampus. In the hypothalamus, doses of 20 mg/kg and 30 mg/kg TMP significantly attenuated up-regulation of TNF-α, IL-1β, and IL-6 mRNA induced by the LPS injection. In addition, TMP (30 mg/kg) significantly reduced the number of COX-2 positive cells in the hypothalamus, Conclusion : These results indicate that TMP has an anti-inflammatory effect on neuroinflammation, especially in the hypothalamus, induced by LPS i.c.v. injection and suggest that TMP-containing Ligusticum wallichii may play a modulatory role on the systemic responses following hypothalamic inflammation.