Objective To investigate the changes of microglia and astrocyte in the substantia nigra of the rat models of Parkinson disease induced by 6-hydroxydopamine(6-OHDA). Methods Adult Sprague-Dawley rats were microinjected with 6-OHDA solution(8μl, 2mg/L) into the substantia nigra and medial forebrain bundle of the right side of the brain. After 2 weeks，there were 16 model rats, sixteen PD rats were randomly divided into two groups： 2-week and 8-week group, 8 in each group. Six adult normal rats were injected saline instead of 6-OHDA as the control group. Two weeks or 8 weeks later,the morphological changes of the dopaminergic neuron(tyrosine hydroxylase positive, TH-positive), the OX-42(specific marker for microglia)positive and GFAP(specific marker for astrocyte)positive in rat substantia nigra were examined by using immunohistochemical and immunofluorescent methods. Results There were only a few TH-positive cells in the 6-OHDA injected side of the model group. The differences between the ratios of the TH-positive cells of 6-OHDA injected side to the normal side in the two model groups and to the both sides in the control group were significant, respectively( P<0.01). There was no difference between the ratios of the two model groups( EM>P/EM>>0.05). The differences between the ratios of the number of the OX-42-positive cells and GFAP-positive cells between the 6-OHDA injected sides and the normal side in the two PD model groups are significant, respectively( EM>P/EM><0.01). The cell bodies of the OX-42-positive cells in 6-OHDA injected sides were ameboid in two PD model groups, and the processes of the GFAP-positive cells in 6-OHDA injected sides of the two model groups became shorter and deepen in color. There was no difference between the the ratios of those of the two model groups( EM>P/EM>>0.05). Conclusion The activation of microglia and astrocyte in the substantia nigra in Parkinson disease model by microinjection of 6-OHDA solution had been showed both in 2-week and 8-week model groups. There were no differences between the activation level of microglia and astrocyte in different time(2-week and 8-week mod