Objective: To study the effects and mechanism of homocysteine(Hey) on Parkinson's disease(PD) induced by 6-hydroxydopamine (6-OHDA) in vivo. Methods:Forty rats were divided into 4 groups. 6-OHDA or the solvent of 6-OHDA was focally administrated to induce PD, 2 h later Hey or 0.9% sodium chloride was administrated in the ipsolateral substantial nigra(SN). We used behavioral testing, Immolunohistochemical techniques, biochemistry techniques to detect the injury of SN. Results:The rotary turns of PD rats induced by 6-OHDA showed significant increase after treatment with Hey compared with the controls(P ＜ 0.05). Also the numbers of tyrosine hydroxylase(TH)-stained neurons were decreased, and dendrites were fragmented and truncated. Free radicals were increased and antioxidant enzymes decreased. Conclusion:Focal infusion of Hey into the SN increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration, it seems that the endangering effect of Hey is due to exacerbating oxidative stress.