Microplastics (MPs), defined as plastic particles smaller than 5 mm, are an emerging class of environmental contaminants. Widely distributed in air, water, and soil, they can enter biological systems mainly through ingestion and inhalation. The first detection of MPs in human blood was recently reported, confirming their ability to cross the epithelial barriers and circulate systemically. These findings raise significant concerns about the potential physiological impacts of MPs' exposure in humans. Therefore, this study aimed to evaluate the effects of subchronic oral exposure to polystyrene microplastics (PS-MPs) on hematological parameters in a mouse model. Male Swiss albino mice were randomly assigned to a control group or an experimental group that received 1 μm PS-MPs suspended in drinking water at a dose of 0.01 mg/day for four weeks. Blood samples were collected weekly and analyzed for complete blood count (CBC) parameters to assess potential alterations in hematological profiles. Exposure to PS-MPs resulted in a progressive decline in several hematological parameters. Notably, reductions in granulocyte count (Gran#), monocyte count (Mon#), monocyte percentage (Mon%), and mean platelet volume (MPV) were observed after the first week. On the fourth week, decreases in red cell distribution width (RDW), platelet count (PLT), and plateletcrit (PCT) were recorded. In contrast, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly elevated, suggesting alterations in erythrocyte morphology and hemoglobin content. The findings of this study demonstrated that subchronic oral exposure to PS-MPs can induce significant alterations in hematological parameters in mice. The observed shifts in leukocytes and erythrocytes suggest impaired hematopoiesis, potential inflammatory responses, and disruptions in blood homeostasis. These results highlight the capacity of MPs to affect systemic physiology and underscore the need for further research into their short- and long-term health impacts, particularly concerning immune and hematological function in both animals and humans.