In the present study, using fast cyclic voltammetry (FCV), atomic absorption/flame emission spectrophotometry and immunohistochemistry, we investigated the correlation between iron levels and degeneration of dopaminergic neurons in rat nigrostriatal system during the early 6-OHDA lesions in the medial forebrain bundle (MFB). The results showed that 1 d or 3 d after lesions in MFB, there was a 45% or 66% reduction, respectively, in the density of tyrosine hydroxylase (TH) immunoreactive cells in the substantia nigra (SN) of the lesioned side accompanied by an increase in iron staining intensity and iron concentration; while there was no change in dopamine (DA) release in the striatum (Str) of the lesioned side compared with the unlesioned side and the normal rats. There was no difference in the iron staining and concentration of SN and DA release of Str on the lesioned side between one-day group and three-days group. These results suggest that an iron level elevation in SN may be involved at the early stage of degeneration of DA neurons in SN. However, DA release in Str was unchanged due to the immense compensatory mechanism of DA system.