The early changes in iron level and neuronal loss in rat nigrostriatal system were investigated using 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats. The results showed that: 1, 3, 5, 7, and 14 days of postlesion, there was a progressive reduction in the density of the tyrosine hydroxylase immunoreactive (TH-ir) cells in the lesioned substantia nigra (SN). Iron level increased in the lesioned SN from 1-14 days following 6-OHDA lesions, but there were no differences in iron level among them. Only on 14 days of postlesion, did the DA release decrease in striatum (Str) of the lesioned side, while there were no changes in other groups. These results implied that the increased iron level in SN occured when there was a moderate reduction of DA neurons. However, the DA release in Str was unchanged until TH-ir cells were highly reduced due to the immense compensatory mechanism of the DA system.