Chokeberry, Aronia melanocarpa, is an indigenous fruit from North America used as food and to prevent chronic disease by Indigenous Peoples. The objective of this study was to test anti-inflammatory effects of anthocyanin on palmitic acid (PA)-induced IL-6 gene expression, IL-6 DNA methylation, and histone (H3) acetylation. Additionally, we examined effects of anthocyanins Cyanidin-3-O-galactoside (C3Gal) and Cyanidin-3-glucoside (C3G) on IL-6 gene expression. Human primary pre-adipocytes were treated with chokeberry juice extract (CBE), C3Gal or C3G in the presence or absence of PA or lipopolysaccharide (LPS). CBE inhibited LPS- and PA-induced IL-6 mRNA expression (p < 0.0001), while C3G and C3Gal had smaller effects. Human IL-6 promoter DNA methylation was increased (p = 0.0256) in CBE treated cells compared to control. Histone H3 acetylations were not affected by CBE or PA treatment. These data indicate that CBE epigenetically reduced PA-induced inflammation by regulating IL-6 DNA methylation without affecting histone modifications in human preadipocyte cells.