The aim of this study was to determine the histological characteristics of the thyroid gland in ApoE KO-/- mice following the application of levothyroxine (l-thyroxine). A total of 12 female ApoE KO-/- mice were divided into two groups. A control group of mice received distilled water and the experimental group received l-thyroxine dissolved in drinking water at a daily dose of 2 µg/ml, over 12 weeks. The paraffin sections were processed with the usual haematoxilin-eosin technique of staining. Qualitative histological analysis demonstrated: the presence of large distended follicles in the peripheral areas of the gland; fulfillment of the lumen of follicles with an ample amount of colloid; complete absence of resorptive vacuoles in the colloid; a flattened follicullar epithelium. Morphometric assessment showed a significant increase in the diameters of follicles in the peripheral areas of the gland and a significant decrease in the height of the follicullar epithelium (p<0,001). Our results demonstrated that l-thyroxine causes characteristic morphological changes in the structure of the thyroid gland in the direction of the occurrence of hyperthyroidism.