The effects of blueberry extract (BE) were investigated on activities of p38 mitogen-activated protein kinase (MAPK) and extracellular extracellular signal regulated kinase 1/2 (ERK1/2) in mouse BV-2 microglia stimulated lipopolysaccharide (LPS). BV-2 microglia were cultured for 24 h in the presence of 1 ${mu}g/mL$ LPS either with or without BE preincubation for 0, 1, and 12 h. BE relieved repression of cell proliferation, and reduced cell death. These alterations caused by BE addition accompanied reduction of radical oxygen species (ROS). There were also significant decreases in the levels of both transcripts, and proteins of inducible nitric oxide synthase (iNOS) and peroxiredoxin 1 (Prx1) genes in the BE-treated cells, suggesting that BE inhibit the ROS-induced gene expression. The antioxidant effects of BE appeared to involve p38 MAPK and ERK1/2 signaling pathways since BE reduced both kinase activities by inhibiting phosphorylation. Taken these results together, BE protects LPS-stimulated BV-2 microglia by reducing cell death, ROS accumulation, and activities of p38 MAPK and ERK1/2.