Background: Although peripheral blood mononuclear cells (PBMC) have been demonstrated to be in a pro-inflammatory state in obesity and type 2 Diabetes Mellitus (T2DM), characterization of circulating PBMC phenotypes in the obese and T2DM and the effect of Metformin on these phenotypes in humans is still ill-defined and remains to be determined.Methods: Thirty normal healthy adult volunteers of normal weight, 30 obese subjects, 20 obese newly diagnosed diabetics and 30 obese diabetics on Metformin were recruited for the study. Fasting blood samples were collected and PBMC were isolated from whole blood. Polarization markers (CD86, IL-6, TNFα, iNOS, CD36, CD11c, CD169, CD206, CD163, CD68, CD11b, CD16, and CD14) were measured by RT-qPCR. Gene expression fold changes were calculated using the 2−ΔΔCT method for RT-qPCR.Results: Obesity and T2DM are associated an increased CD68 marker in PBMC. mRNA expression of CD11b, CD11c, CD169, and CD163 were significantly reduced in PBMC from T2DM subjects whereas CD11c was significantly inhibited in PBMC from obese subjects. On the other hand, macrophage M1-like phenotype was observed in T2DM circulation as demonstrated by increased mRNA expression of CD16, IL-6, iNOS, TNFα, and CD36. There were no significant changes in CD14 and CD86 in the obese and T2DM when compared to the lean subjects. Metformin treatment in T2DM reverted CD11c, CD169, IL-6, iNOS, TNFα, and CD36 to levels comparable to lean subjects. CD206 mRNA expression was significantly upregulated in PBMC of T2DM while Metformin treatment inhibited CD206 expression levels.Conclusions: These data support the notion that PBMC in circulation in T2DM express different pattern of phenotypic markers than the patterns typically present in M1 and M2 like cells. These phenotypic markers could be representative of metabolically activated macrophages (MMe)-like cells. Metformin, on the other hand, reduces MMe-like cells in circulation.