Abstract: Iron overload leads to progressive organ dysfunction, with the liver serving as the primary site of deposition due to the absence of a physiological elimination pathway. The regulation of systemic iron homeostasis depends on proteins such as hepcidin (Hamp), ferritin light chain (Ftl), and transferrin receptor 1 (Tfr1). This study evaluated hepatic expression of Hamp, Ftl, and Tfr1 in normal rats and assessed the effect of Deferiprone (DFP) in an iron overload model. Eighteen male Wistar rats (150–200 g) were randomized into three groups (n = 6 each): normal (N), iron overload (NC; iron dextran 120 mg/kg body weight, intravenously, over 15 days), and treatment (T; iron dextran + DFP 100 mg/kg body weight/day orally for 28 days). Gene expression was analyzed by RT-PCR and quantified using the Livak method. Iron overload significantly upregulated Hamp and Ftl while downregulating Tfr1 compared with controls. DFP administration reversed these effects, reducing Hamp and Ftl expression while restoring Tfr1 to near-normal levels. These findings suggest that DFP modulates hepatic iron-regulatory genes, supporting its therapeutic potential in managing iron overload.