Polyphenols are known to protect against cardiometabolic diseases although very few studies have been carried out in the context of a food matrix. We fed ApoE-/- mice with diets containing standard red tomatoes or tomatoes expressing different polyphenols. Mice were sacrificed by exsanguination under isoflurane and perfused with 0.9% Saline and EDTA via cardiac puncture. Effects of the diets on aortic sinus plaque size and macrophage infiltration were determined using immunohistochemistry, fluorescent microscopy and quantification using ImageJ and Gene expression by qRT-PCR. The effects of anthocyanin metabolites, resveratrol and resveratrol phase II conjugates on the expression of genes involved in inflammation and Reverse Cholesterol Transport (RCT) were determined in PMA differentiated THP1 macrophages. All gene expression experiments were repeated at least three times. Data were not normally distributed, so Mann Whitney test was used with Holm adjustment for multiple comparisons as outlined by Chen et al 2017. Data are presented as medians (Mdn). Aortic sinuses of mice fed flavonols + anthocyanins (Mdn = 14.21, n =19) and those expressing resveratrol (Mdn = 15.02, n = 19) had significantly reduced plaque sizes compared to those fed the red tomato control diet (Mdn = 18.73, n = 20), U = 94.50, P = 0.008 and U = 101.0, P = 0.0129 respectively. In comparison to controls (Mdn = 9.276, n =11), mice on the flavonol + anthocyanin diet (Mdn = 4.878, n =11) but not the resveratrol diet (Mdn = 7.804, n =11) had reduced aortic sinus macrophage infiltration U = 30, P = 0.05 and U = 52.00, P = 0.60 respectively. Diets supplemented with tomatoes expressing flavonols or isoflavones alone had no effect on plaque size, nor did they influence macrophage infiltration. In THP1 macrophages, in the absence of TNF-α as an inflammatory stimuli an anthocyanin metabolite phloroglucinaldehyde (PGA) significantly increased ABCA1 gene expression (Mdn = 2.0 vs 1.0 in controls), U = 1.0, P = 0.001 and decreased ABCG1 (Mdn = 0.66 vs 1.02 in controls), U= 4, P = 0.001, PGA also increased TNF-α gene expression (Mdn = 4.171 vs 0.96 in controls), U = 0.0, P = 0.001. In contrast, resveratrol increased ABCG1 gene expression both in the absence (Mdn =1.77 vs 1.1 in controls), U = 2, P = 0.001 and in the presence (Mdn =2.2 vs 0.96 in controls), U = 0.0, P = 0.001) of TNF-α. In the presence of TNF-α resveratrol also reduced gene expression of TNF-α (Mdn = 0.34 vs 1.3 in the controls), U = 0.0, P = 0.001 and IL-10 gene expression (Mdn = 0.36 vs 1.4 in the controls) U = 0.0, P = 0.001. Thus, in the context of tomato food matrix, anthocyanins and resveratrol may act through differential pathways involving macrophage infiltration and reverse cholesterol transport to reduce atherosclerotic plaque development.