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Microflora in the gastrointestinal tract plays an important role in the hepatocyte function from the gut-liver axis. However, the effect of probiotic in innate immune response especially in Kupffer cells is still unclear. This study aimed to examine the effect of probiotic on the innate immune response in the liver. This study is a randomized posttest-only control group experimental animal study using white mice (Mus musculus BALB/c). The inclusion criteria are 10-12 weeks old, male, and weighing 30-40 mg. Samples were randomized and divided into two groups: probiotic and placebo. The probiotic group was given multispecies probiotic. Probiotic and placebo were administrated for 21 days via a gastric tube. On day 22, necropsy was performed, and liver was obtained for immunohistochemical examination at the Laboratory of Biochemistry, University of Brawijaya, Malang. Number of Kupffer cells and cells which expressing NF-κ B p105 and p65 were examined. A total of 16 mice met the inclusion criteria. A significant increase in the number of Kupffer cells (p<0.001) and NF-κ B p105 (p=0.001) was observed after administration of probiotic. No significant differences were observed in NF-kB p65 (p=0.236). Administration of probiotics affects the innate immune response (NF-κ B p105 and Kupffer cell) in the liver tissue but not in NF-κ B p65. [ABSTRACT FROM AUTHOR]