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Background: Regarding the immunomodulatory effects of lactobacillus bacteria, this study aimed to evaluate the effect of oral administration of Lactobacillus reuteri, as probiotic bacteria, on natural killer cell cytotoxicity and tumor-specific lymphocyte proliferation in Balb/c mice with breast adenocarcinoma. Methods: A total of 30 female mice, aged 6- 8 weeks and with a weight of approximately 17- 19 g, were randomly divided into two groups of 15 mice. The case group received Lactobacillus reuteri at a dose of 2.7× 108 bacteria in half a milliliter of sterile phosphate buffer saline (PBS) and the control group only received PBS. The probiotic group received the regimen for two weeks prior to tumor transplantation, as they did for 30 days after transplantation with three-day intervals and durations of seven days. For the evaluation of natural killer cell cytotoxicity and also tumor-specific lymphocyte proliferation response, LDH and BrdU assays were performed respectively according to the manufacturers' instructions. Results: The study showed that the mice in the case group which were receiving Lactobacillus reuteri had statistically significant differences in the replication of tumor -specific lymphocytes, natural killer cell cytotoxicity and delayed hypersensitivity responses Compared to the mice in the control group. Conclusion: Daily consumption of probiotics seems to regulate the immune system and consequently it can be helpful in people with cancer. Moreover, consumption of probiotics in healthy individuals can also boost the efficiency of the immune system against a variety of abnormalities.