To study the effect of Guiling Pa'an Pill on the expression of transcription factor EB(TFEB) in the treatment of Parkinson's disease(PD) and its mechanism.Methods:The PD rat model was randomly divided into model group，western medicine group，traditional Chinese and western medicine group and traditional Chinese medicine low，middle and high dose groups，with 15 in each group.Another 15 normal rats were selected as sham operation group.The model group and sham operation group were given same volume of normal saline，and the other groups were given corresponding medicines by intragastric administration for 4 consecutive weeks.After the PD rats were sacrificed，the substantia nigra of the midbrain was collected.The protein expressions of TFEB，microtubule-associated protein light chain 3Ⅱ(LC3Ⅱ)，P62，tyrosine hydroxylase(TH) and α-synuclein(α-syn) were detected by Western Blotting.Results:Compared with the conditions in sham operation group，the protein expressions of TFEB，LC3Ⅱ and TH in the substantia nigra of the model group，western medicine group，traditional Chinese and western medicine group and traditional Chinese medicine groups decreased significantly(P<0.01)，while the protein expressions of P62 and α-syn increased significantly(P<0.01).Compared with the model group，the western medicine group，traditional Chinese and western medicine group and traditional Chinese medicine groups had up-regulated TFEB，LC3Ⅱ and TH in substantia nigra(P<0.01)，while down-regulated P62 and α-syn(P<0.01).Conclusion:Guiling Pa'an Pill can activate autophagy-lysosome system through TFEB，enhance the autophagy of neural cells，increase LC3Ⅱ and TH，and promote the degradation and clearance of α-syn and P62，thereby playing a neuroprotective effect.