OBJECTIVE To explore the role of 26 S proteasome and nuclear factor kappa B (NFκB) in substantia nigra in the management of Parkinson's disease (PD) by acupuncture. METHODS Forty-eight male SD rats were randomly divided into normal, sham operation, model and electroacupuncture (EA) groups (12 rats/group).. The PD model was established by 40-day consecutive subcutaneous injection of rotenone (1 mg/kg dissolved in dimethyl sulfoxide and normal saline) at the back shoulder. The rats in the sham operation group were treated by subcutaneous injection of dose of saline. "Fengfu" (GV 16) and "Taichong" (LR 3) acupoints were stimulated with EA at 2 Hz, 1 mA, 20 min of duration in each treatment, and daily for 28 consecutive days. The behavioral changes of rats in each group were measured and scored at 40th day and 68th day, respectively. Immunohistochemistry was used to determine the expression of tyrosine hydroxylase (TH) used to detect the expression of 26 S proteasome and NFκB and TH were measured by Western blot. RESULTS In comparison with the normal and sham operation groups, the behavioral scores of rats in the model group were elevated, which were significantly decreased by EA intervention (P < 0.05). The expression of TH and 26 S proteasome decreased whereas the NFκB increased in the rats of model group (P < 0.05); and EA intervention reversed these changes (all P < 0.05). CONCLUSION EA intervention can improve PD rats' behavioral changes, which is pobably related to its effects in reducing loss of TH-positive neurons, down-regulating NFκB protein expression, and up- regulating 26 S proteasome protein expression in the substantia nigra.