Abstract Locust bean gum (LBG) is a galactomannan extracted from the seeds for use as a food thickener and stabilizer and is claimed to have applications in the biopharmaceutical field. The possible immunomodulatory effects of LBG have been studied in cell lines. The objective of this study was to evaluate the effect of LBG on the expression of genes associated with innate and adaptive immune responses in cow blood. Blood was collected from (n=3) clinically healthy Holstein-Friesian cows from the North Carolina A&T State University Dairy Unit. Whole blood (1 mL) from three cows was treated individually with 10 ng/mL of LBG (Sigma-Aldrich St. Louis, MO) or maintained in PBS, incubated at 37ºC for 30 minutes. Total RNA was extracted, reverse transcribed, and real-time PCR was carried out using the RT2 Profiler human Innate & Adaptive Immune Responses PCR Array containing 84 genes, as recommended by the manufacturer (Qiagen). The Livak method was used to calculate fold change (FC >2 considered significant). The analysis showed that 40 genes out of 84 genes were affected by treatment with LBG. Among 40 genes, 4 were upregulated, and 17 genes were downregulated. The highest up-regulated and down-regulated genes following exposure to LBG were Metaxin 1(MX1) and Recombination activation gene 1 (RAG1) respectively. The MX1 gene, which encodes a protein located on the outer membrane of mitochondria, is a component of the mitochondrial protein translocation apparatus. The RAG-1 gene is involved in the activation of immunoglobulin V-D-J recombination and immune homeostasis. Thus, gums may have bioactive roles in cow blood. The observed differential effects seen have implications for the function of the molecules examined possible epigenetic regulation of V(D)J recombination and potential for dietary modulation of animal health using gums and dietary fiber and warrant further study.