Abstract: To investigate the effects of VHL (von Hippel-Lindau) inhibitor on Caenorhabditis elegans (C.elegans) model of Parkinson''s disease (PD),C.elegans were exposed to rotenone and treated with VHL inhibitor VH298.The death,dopaminergic neurodegeneration and mitochondrial unfolded protein response (mito-UPR) of transgenic strains with the markers zcIs9 and otIs181 exposed to different concentrations of rotenone were investigated. The death,dopaminergic neurodegeneration,and changes of behaviors including head thrashes,body bends and foraging behavior of C.elegans model of PD treated with different concentrations of VH298 were explored.The results showed that different concentrations of rotenone can lead to the death,dopaminergic neurodegeneration and abnormal mito-UPR of transgenic nematodes with zcIs9; otIs181,while the VHL inhibitor can decrease the death rate and alleviate dopaminergic neurodegeneration of rotenone-induced C.elegans model of PD.The VHL inhibitor can also attenuate the behavioral abnormalities of head thrashes,body bends and foraging behavior of C.elegans model.These results suggest that rotenone may cause mitochondrial damage in the transgenic nematodes with zcIs9; otIs181, and then destroy mitochondrial homeostasis,thereby resulting in dopaminergic neurodegeneration and death of the nematodes. The VHL inhibitor VH298 may promote the survival of rotenone-induced C.elegans model of PD,and alleviate dopaminergic neurodegeneration,thereby improving the behavioral abnormalities of C.elegans model of PD.