Atherosclerosis is a complex inflammatory process associated with high-mortality cardiovascular diseases. Today, there is a growing body of evidence linking atherosclerosis to mutations of mitochondrial DNA (mtDNA). But the mechanism of this link is insufficiently studied. Atherosclerosis progression involves different cell types and macrophages are one of the most important. Due to their high plasticity, macrophages can demonstrate pro-inflammatory and pro-atherogenic (macrophage type M1) or anti-inflammatory and anti-atherogenic (macrophage type M2) effects. These two cell types, formed as a result of external stimuli, differ significantly in their metabolic profile, which suggests the central role of mitochondria in the implementation of the macrophage polarization route. According to this, we assume that mtDNA mutations causing mitochondrial disturbances can play the role of an internal trigger, leading to the formation of macrophage M1 or M2. This review provides a comparative analysis of the characteristics of mitochondrial function in different types of macrophages and their possible associations with mtDNA mutations linked with inflammation-based pathologies including atherosclerosis.