ABSTRACT: Obesity and its consequences on cardiometabolic health have been associated to low-grade inflammation. The most diverse source of dietary anti-inflammatory compounds is polyphenols and especially anthocyanins, which are major polyphenols in bilberries (Vaccinium myrtillus). We investigated the effects of a bilberry-rich diet on glucose and lipid metabolism, inflammation and gene expression profile in peripheral blood mononuclear cells (PBMCs) in subjects with overweight and other features of the metabolic syndrome. The study was a randomized, controlled clinical intervention using 2-arm parallel group design. The participants in the bilberry group (BB, n = 15) consumed bilberries or berry products equivalent of 400 g fresh bilberries daily for 8 weeks, while the participants in the control group (C, n = 12) were asked to maintain their habitual diet. The microarray profiling was done from 3 subjects in the BB group and further QPCR expression analyses from all subjects in both groups at the start and end of the intervention (weeks 0 and 8). From 50 differentially expressed transcripts (P<0.005), five candidate genes; WDSUB1, COX7B, RGS18, DAPP1 and TICAM1, were randomly selected for QPCR analyses from PBMCs in both groups. To further explore the interplay of dietary change and activated pathways in PBMCs, 11 additional genes were selected for QPCR. The selected transcripts were from the LPB, RIPK-1, Ly96 (MD2), CD19, MMD, TNFRSF12A, CD72, CCR2, IL17RC, IL17R and MAP3K7IP2 genes. Our results indicate that regular bilberry intake may reduce endotoxemia and chronic inflammation, the latter especially by directing the immunity away from overactive innate cell mediated responsiveness. Bilberry consumption may decrease cardiovascular and metabolic risk in the long term. The microarray profiling was done in PBMCs from 3 subjects in BB group and further QPCR expression analyses in PBMCs from 15 subjects in the BB group and 12 subjects in the C group. For QPCR expression analyses; Time point (biological replicate): 0 wk: baseline PBMCs1 - 15, baseline PBMCc1- 12 Time point (biological replicate): 8 wk: bilberry PBMCs1 - 15, bilberry PBMCc1 - 12 Non-normalized data with triplicate samples (technical replicate) of each bilogical replicates (replicate1-3)