The present study was conducted to address how high-fat diet (HFD)-induced metabolic syndrome (MetS) makes alterations to murine hematological profile. Fasting plasma glucose (FPG) of 80 male NMRI mice was measured and mice with FPG falling within the range of 80-160 were included as healthy or non-diabetic mice. Afterward, mice in the selected population were categorized into two separate main groups including normal control (NC, n = 32) and HFD -induced MetS (n = 32) having received a normal chow diet and a HFD, respectively, and 8 mice sacrificed for a biochemical and hematological profile at weeks 2, 4, 8, and 16. Lipid profiling, peripheral blood analysis, and bone marrow (BM) interpretation were considered endpoints. Results were analyzed in a separated time panel using a non-paired t-test at the significance level of p˂0.05. Gained weight at week 16, increased accumulation of abdominal fat at week 8, raised FPG at weeks 2 and 8 and increased high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) at week 8 were observed in MetS compared to NC group confirming successful translation of a murine model of MetS. Hematologically, no change in serum ferritin, serum iron, hematocrit, platelet count, and differential leukocyte count (DLC) was observed in MetS compared to NC group. By contrast, MetS group showed raised absolute basophil count compared to NC group at week 8. Strikingly, MetS group showed a downward trend in hemoglobin concentration compared to NC group. However, this downward trend was only significant in the 2nd week. In addition, mean corpuscular volume and mean corpuscular hemoglobin in MetS group dropped at week 8 compared to NC group. Furthermore, MetS group showed decreased erythroid lineage cells including proerythroblast, polychromatophilic erythroblast, and orthochromatophilic erythroblast proposing the presence of anemia in the murine model of MetS. Histopathologic evaluation of BM showed decreased cellularity and increased infiltration of lipids in MetS compared to NC group. Additionally, MetS group showed the reduced number of basophils, eosinophils, and monocytes in BM during the first 8 weeks of the study. However, in the 16th week, lymphocytes were the only decreased cells, and the absolute count of neutrophils, basophils, and monocytes was raised possibly towards higher production of inflammatory cells in MetS group. It is worth noting that change in the number of plasma cells was shown to be highly variable throughout study. Following the successful development of a HFD-induced murine model of MetS, histological examination of BM in MetS mice showed reduced cellularity and enhanced accumulation of adipose tissue. Additionally, BM analysis indicated significantly decreased basophils, eosinophils, and monocytes at early weeks of receiving diet; however, increased neutrophils, basophils, and monocytes were observed at the end of the study which can primarily be considered reactive leukocytosis due to MetS-mediated inflammatory response. Furthermore, enumeration of erythroid lineage cells in BM demonstrated a significant decrease in proerythroblasts, polychromatophilic erythroblasts, and orthochromatophilic erythroblasts, highly suggestive of anemia
