Background: Activated microglial cells are found in different sorts of the neurodegenerative process including Parkinson and Alzheimer. Suppressing the activated microglial cells developed as a novel procedure for the treatment of neuroinflammation-based neurodegeneration. Materials and Methods: We have investigated the effects of simvastatin on memory impairment and inflammatory cytokines expression induced by transient cerebral ischemia in cultured microglial cells. Results: The lipopolysaccharide (LPS)-activated microglial cells treated with simvastatin 3 μmol has decreased the inflammation which was indicated by the reduced levels of the nitric oxide (NO), tumor necrosis factor-α, interleukin-1 β, cyclooxygenase-2, and inducible NO synthase. Simvastatin also delayed the activation of atomic component nuclear factor-κB, p38 mitogen-activated protein kinase, and the reactive oxygen species in LPS-activated microglial cells. Moreover, simvastatin has provoked the outflow of heme oxygenase-1 in BV-2 microglial cells. Conclusions: The present study showed that the simvastatin antagonizes neuroinflammation and can be a potential restorative operator for treating neuroinflammatory ailments.