Objective To study the effect of proteasome on nigral degeneration and Lewy body formation. Methods By stereotaxic unilateral injection of different doses of lactacystin, a selective proteasome inhibitor, into the substantia nigral pars compacta of rats, the spontaneous and apomorphine induced contralateral behaviors of rats were observed. Nigral degeneration and Lewy body were viewed by HE staining; expressions of ? synuclein and tyrosine hydroxylase in nigral cells were investigated by immunohistochemistry. Contents of dopamine and homovanillic acid were determined by HPLC. Results There were no difference between 0 2 ?g group and control. Animals treated with 2 ?g and 8 ?g lactacystin developed progressively bradykinetic and displayed contralateral head tilting and tremor; apomorphine induced contralateral behavior was notably observed in rats of 8 ?g group; 3 weeks later, nigral degeneration were present in 2 ?g and 8 ?g groups; some of nigral cells contained acidophilic Lewy body with intense immune response to ? synuclein; the number of tyrosine hydroxylase positive cells in 2 ?g and 8 ?g groups were decreased by 68 24% ( P