Mitochondria are important for cellular function, and as cells divide, their mitochondria also divide by replicating their DNA. The integrity of mitochondria DNA (mtDNA) replication, carried out by Polymerase G (PolG), is critical for the maintenance of mitochondria and their cellular functions. In this study, I use mice carrying a mutant PolG, PolGD257A, to determine the effect of increased mtDNA mutations on the macrophage population and polarization in response to bacterial and cytokine challenge. I hypothesized that increased mtDNA mutations will suppress the ability of macrophages to clear pathogens. To test this hypothesis, I used the PolGD257A mice, along with Listeria monocytogenes (LM) as a model of bacterial infection. Three days post LM infection, the bacterial load and the macrophage population were determined in the spleen and liver of PolGD257A and WT mice. No statistical difference was observed in the bacterial load in the liver or spleen, or in the macrophage population in the spleen of the PolGD257A and WT mice. However, I found that PolGD257A/D257A mice are associated with a higher percentage of macrophages in the liver during LM infection. Polarization of peritoneal macrophages into classically activated (M1) and alternatively activated (M2) macrophages was also studied in vitro. In a single experiment, I found that increased mtDNA mutations in PolGD257A mice seemed to elicit increased M1 and decreased M2 macrophage polarization. Replication of the experiment is warranted to confirm these results. The findings from these experiments could lead to a better understanding of the role of the mitochondria and macrophages in infectious disease.