Blueberry extract (BE) is rich in phenols, especially anthocyanins. Anthocyanins regulate the inflammatory response in mice and may be related to gut microbiota and bile acid receptors. The aim of the present study was to explore the effects of BE on the inflammatory response by regulating gut microbiota and bile acid receptors in mice administered Escherichia coli lipopolysaccharide (LPS). Thirty male KM mice were randomly divided into three groups: CON (control diet) group; LPS (LPS stimulation) group; and LPS + BE (LPS stimulation, 5% BE intervention) group. our results showed that, compared with the LPS group, the addition of BE decreased the level of inflammatory factors in serum and tissues, inhibited the TLR4/MyD88 signaling pathway, protected the intestinal barrier and activated FXR/TGR5, which was related to gut microbiota (especially Akkermansia). The active component (e.g., cyanidin 3-O-glucoside, C3G) in BE may be an important factor in regulating gut microbiota. BE alleviated the inflammatory response mainly by activating bile acid receptor expression and regulating the gut microbiota; this effect may be related to the composition of bioactive substances in BE. © 2023 Society of Chemical Industry.