Synthetic fabrics, especially polyester, are a primary source of microplastic fibers (MFs), but there is limited data on their accumulation and dose related health impact in living organisms. This study examined the effects of ingested polyester microfibers (PE-MFs) on hematology, histopathology, and serum biochemistry in albino mice. Mice were given varying doses of PE-MFs (100, 200, 400 and 800 μg/d/mice) for a duration of thirty-five days and a notable decreases in certain hematological parameters such as RBCs, Hb, and platelets, and increases in MCV and MCH was noted at (p < 0.05) thereby indicating possible inflammatory response within the body resulting from ingestion of these MFs. Liver enzymes (ALT, AST, and alkaline phosphatase) and histopathological changes in the liver and gastrointestinal tract also exhibited significant variations, with higher levels seen in the group receiving the highest dose of PE-MFs (800 μg/d/mice). In summary, increased exposure to PE-MFs led to a dose-related impact and notable alterations in histopathological, hematological, and serum biomarkers in albino mice. This study highlights the potential hazards associated with dietary exposure to PE-MFs in mammals and emphasizes the need for further research in this field.