Objective To investigate the possible action mechanism of Nourishing-Kidney Formula in the treatment of Parkinson’s disease（ PD）. Methods A total of 40 male Sprague-Dawley rats were injected with subcutaneous injection of rotenone sunflower oil emulsion to establish a PD rat model. They were randomly divided into low

medium and high doses of Nourishing-Kidney Formula（ 40

80

160 mg/kg Nourishing-Kidney Formula decoction）and a model group（ equal volume saline by gavage）

with 10 rats in each group. There were also 10 rats in the normal group and the solvent group（ equal volume saline by gavage）. The suspension experiment was performed on the14 th day of intragastric administration; the number of black tyrosine hydroxylase（ TH） positive cells was detected by immunohistochemistry

and the striatum

frontal lobe dopaminergic neurotrophic factor（ CDNF） and midbrain glial cell-derived neurotrophic factor（ MANF） protein were detected by Western Blot. RT-PCR was used to detect the expression of CDNF and MANF mRNA in striatum and frontal lobe. Results Compared with the model group

the suspension test scores in the middle and high dose groups of Nourishing-Kidney Formula increased

and the number of TH cells in the substantia nigra increased. The CDNF protein expression in the striatum and frontal striatum

and the MANF protein and mRNA levels in the striatum of the high-dose Nourishing-Kidney Formula group

the levels of CDNF mRNA in the striatum and the expression of MANF mRNA in the frontal lobe were also significantly increased.The expression of CDNF mRNA in the frontal lobe of each group was increased（ P < 0. 05 or P < 0. 01）. Conclusion Nourishing-Kidney Formula can improve the behavioral disorder of Parkinson’s disease and protect the dopaminergic neurons of striatum and frontal lobe. The protective effect may be achieved by correcting the expression of CDNF and MANF in different brain regions

and it is better to use high dose.