Objective:To investigate the relationship between TLR2/NF-κB signaling pathway and the apoptosis and autophagy dysfunction of RSC96 cells induced by 1-methyl-4-phenyl-pyridinium(MPP+ ). Methods:RSC96 cells were divided into the PBS group, MPP + group,and MPP + + CU-CPT22 group. Cell survival rate was detected using CCK-8 after treatment with different MPP + concentrations(0.1,0.3,0.5,0.7,0.9 mmol/L). Cell apoptosis was detected by TUNEL staining. RT-qPCR was performed to detect the TLR2 mRNA level. Western blot was performed to detect the expression levels of apoptosis related indicators Bcl-2/Bax,cleaved caspase-3/caspase-3,autophagy-related indicators LC3II/LC3I and P62,as well as TLR2 and p-NF-κB/NF-κB. Results:Compared with the PBS group,the cell viability of the MPP + group decreased in a concentration-dependent manner,the number of TUNEL-staining positive cells increased,the ratio of Bcl-2/Bax decreased while cleaved caspase-3/caspase-3 ratio increased,as well as had a decrease in the ratio of LC3Ⅱ/LC3Ⅰ and an increase in P62 and p -NF -κB/NF -κB ratio elvel. RT -qPCR and Western blot results showed that MPP + upregulated the expression of TLR2. In addition,compared with the MPP + group,the MPP + + CU-CPT22 group showed a decrease in the number of TUNEL-staining positive cells,an increase in Bcl-2/Bax level,and a decrease in cleaved caspase-3/ caspase-3 ratio. Meanwhile,LC3 Ⅱ/LC3 Ⅰ ratio was increased,and the P62 expression level was decreased. Conclusion:MPP + stimulation induced apoptosis and the imbalance of autophagy in RSC96 cells,and the mechanism may be related to the activation of the TLR2/NF-κB signaling pathway.