The aim of the present study was to investigate whether the iron chelator Desferal prevents the degeneration of dopaminergic neurons in the substantia nigra (SN) induced by iron-overload in rats. Using fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high-performance liquid chromatography-electrochemical detection, we measured the degeneration of dopaminergic neurons and increased iron content in the SN of rats overloaded with iron dextran and assessed the effects of treatment with Desferal. The results showed that iron dextran overload increased the iron content in the SN, decreased dopamine release and content, and reduced the numbers of TH-immunoreactive neurons. Treatment with Desferal prevented the increased iron content in the SN. As a result, dopamine release and content remained at almost normal levels, while the numbers of TH-immunoreactive neurons remained at control values. This study suggests that the iron chelator Desferal is neuroprotective against iron-overload, so iron chelators that can cross the blood-brain barrier may have the potential to treat cases where abnormal iron accumulation in the brain is associated with the degenerative processes, as in Parkinson's disease.