Background: Obesity has currently been a growing health concern that has ranged across the world. Diet-induced obesity drives gut inflammation through the production of cytokines and alteration in gut microbiota. High-fat diet (HFD) favors the conditions that lead to gut inflammation with an increased gut epithelial permeability, allowing for higher chances of gastrointestinal disorders. Antibiotic usages interrupt gut symbiosis and further exacerbate HFD-induced complications. Evidence indicates that HFD with antibiotics increases the risk of pre-inflammatory bowel disease (IBD). Blueberries contain bioactive flavonoid compounds called anthocyanins which possess antioxidant and anti-inflammatory properties. We assessed whether dietary blueberry improves HFD- and antibiotics-induced gut inflammation. Methods: Male C57BL/6J mice (7 weeks old) were divided into three groups: (1) control mice consumed standard diet (C), (2) mice consumed HFD and treated with antibiotics in drinking water (HFA), (3) mice consumed blueberry supplemented HFD and treated with antibiotics (HFAB) for 12 weeks. Gut inflammation was assessed by measuring the mRNA expression of inflammatory markers (IL-1β, IL-6, iNOS, and MCP-1) using qPCR. The total RNA was isolated from the colon using RNeasy plus mini kit, cDNA was synthesized using RT-PCR kit, and the expression of inflammatory molecules was measured with qPCR using SYBR green (Qiagen). Results & Discussion: The mRNA expression of inflammatory markers IL-1β, iNOS, and MCP-1 were significantly increased in HFA vs. C mice. However, dietary supplementation of blueberries significantly reduced the expression of IL-1β, iNOS, and MCP-1, indicating the beneficial effect of blueberries on the gut. The mRNA expression of IL-6 was similar among the groups. Our ongoing studies focus on identifying the molecular mechanisms involved in the protective effect of blueberries. Our study suggests consumption of blueberries may be a potential dietary approach to improve gut health.