Acanthopanax senticosus, a traditional herb commonly found in Northeastern Asia,has been used for treating neurodegenerative diseases. However, the molecular and cellular mechanisms of its effect on neuroinflammation have not been investigated. In the current study, quantitative proteomics approach was applied to investigate the effect of Acanthopanax senticosus extract (ASE) on nitrosative stress and inflammatory response in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). The results showed ASEinhibited LPS-induced nitric oxide (NO) production, while no significant toxicity appeared in the cells. Proteomic quantitative analyses using 2D-DIGE (Difference in Gel Electrophoresis) combined with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) revealed that 17 proteins showed significant changes responding to ASE. Furthermore, signal transduction pathways and network modulated by the ASE were predicted using Ingenuity Pathway Analysis (IPA). These findings indicated the ability of ASE to suppress LPS-induced nitrosative stress in BV-2 cells, and may provide important insights into the molecular mechanism underlying potentially beneficial effect of Acanthopanax senticosus.