The purpose of this study was to assess the in vivo effects of melatonin, as an antioxidant, on striatal dopaminergic function in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the striatum. Compared with sham-operated controls and expressed as a ratio relative to the contralateral side, there was an increase in the lipid peroxidation product malondialdehyde (MDA, 142%) and a significant reduction in tyrosine hydroxylase (TH) enzyme activity (28%) and dopamine (DA, 32%) and its metabolite dihydroxyphenylacetic acid (DOPAC, 50%) 2 weeks after 6-OHDA injection. Melatonin treatment almost completely restored MDA levels to normal, suggesting the in vivo action of melatonin as an antioxidant. In parallel, partial, but statistically significant recovery of striatal dopaminergic function, including TH enzyme activity and DA levels, also occurred following melatonin treatment. Taken together with our previous reports showing behavioral and histochemical effects of melatonin on the nigrostriatal dopaminergic system, the present results strongly support the hypothesis that melatonin, as an antioxidant, may have beneficial effects on therapeutic approaches for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease (PD).