To evaluate the anti-inflammatory function and underlying genes targeted by bilberry, gene expression profiling through DNA microarray was performed on bilberry extract-treated macrophages. Among 22,050 oligonucleotides, the expression levels of 998 genes were increased by > or = twofold in lipopolysaccharide (LPS)-activated RAW264 cells, 358 gene signals of which were attenuated by bilberry extract (> or = 1.5-fold). Expression levels of 2,086 genes were decreased by > or = twofold in LPS-activated cells, of which 939 gene signals were enhanced by bilberry extract (> or = 1.5-fold). Utilizing Panther group analysis, 308 genes affected by bilberry extract were classified into 43 categories relating to biological processes (97), molecular functions (186), and signaling pathways (26) with > or = 1.5-fold change. The genes categorized as "defense, inflammatory response, cytokines activities, and receptor activities" were further identified, and some of them were confirmed by real-time polymerase chain reaction. The DNA microarray results provide a molecular basis for the anti-inflammatory effects of bilberry.