Parkinson's disease (PD) is a human neurodegenerative disorder that is associated with a massive and progressive degeneration of the dopaminergic neurons of the substantia nigra. There is strong evidence that oxidative stress participates in the etiology of PD. Therefore, we designed this study to investigate the neuroprotective activity of vitamin E, a free radical scavenger in the unilateral model of early PD. For this purpose, 6-OHDA lesioned rats were pretreated with d-α-tocopheryl acid succinate (24 I.U./kg, i.m.) and the treatment continued three times a week for a period of one month. Apomorphine- and amphetamine- induced rotations and the number of the WGA-HRP labeled-neurons in the substantia nigra pars compacta were evaluated as indexes of the treatment efficacy. The results of behavioral tests reveal that there is a very significant reduction in drug-induced contraversive (68%) and ipsiversive (74%) rotations in vitamin E-treated lesion group (L+E) compared with the vehicle-treated lesion group (L+V)(p<0.001 ). Histochemical results indicate that the total number of labelled neurons in the substantia nigra pars compacta show a 30% and 65% decrease in L+E (p<0.05) and L+V groups (p<0.01) respectively compared with the sham group. Taken together, these results suggest that vitamin E is moderately effective in the neuroprotective therapy of Parkinson's disease and may, at least prolong the survival of nigral dopaminergic neurons.