Macrophages can recognize antigens and microorganisms, and then initiate an appropriate defense. However, there has been a lack of comprehensive information regarding the genes that are modulated by commensal yeasts, including Saccharomyces cerevisiae or Saccharomyces exiguus. In addition, it is not clear to what extent the beneficial yeasts modulate the immune response against microbes and/or microbial toxins. Using DNA microarray, which contains approximately 25,000 genes, we studied interactions between host cells and yeast/bacterial toxin (LPS) by analyzing the transcriptional response of macrophages stimulated by Saccharomyces exiguus and/or Lipopolysaccharides. Thirty three genes were identified to be modulated by more than two folds between groups of macrophage cells. Pathway analysis provided insight into the mutual interactions. Of particular interest was the responses elicited by fungus in murine macrophage cells, including modulation of immunity/defense, cellular signal transduction, cell proliferation/differentiation, and transport. This finding indicates that the yeast induces immune response pathways as well as those associated with cell proliferation and transport. Among the 33 genes identified from the DNA microarray screening, eight genes were further checked by RT-PCR analysis using gene specific primers. Compared to those of negative control, sequential treatment with the yeast strain followed by LPS apparently induced expression of Tnfaip3, IL7R, and CD86, while it inhibited expression of Cxcl10 and CD83. In conclusion, this study identified the genes that are up-regulated by Saccharomyces exiguus. A further study is needed in order to determine whether these genes are modulated at the protein level, and also for their roles in control of immune responses.