Objective To investigate the expression of silent information regulator 1 (SIRT1) and hypoxia-inducible factor 1α (HIF-1α) and behavioral changes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice.Methods C57BL/6 mice were treated with MPTP to establish a Parkinson's disease (PD) model. The successful establishment of PD model was confirmed by behavioral test, high-performance liquid chromatography (HPLC), and immunohistochemistry. The expression of SIRT1 and HIF-1α in PD model mice was determined by Western blot.Results The mice treated with MPTP showed significant behavioral abnormalities:reduced autonomic activity, shortened step length, and bradykinesia (all P<0.001). The HPLC results showed that the PD model mice had significantly lower levels of dopamine and its metabolites in the striatum than the control mice (P<0.001). The immunohistochemistry results showed that the levels of tyrosine hydroxylase and dopamine transporter (dopaminergic neuron markers) in the substantia nigra of PD model mice were significantly down-regulated (P<0.01). The PD model mice had a significantly lower level of SIRT1 and a significantly higher level of HIF-1α compared with the control mice (P<0.05). Conclusions The PD model mice have significant behavioral abnormalities. The decrease in levels of dopaminergic neuron markers suggests that the PD model is successfully established. The abnormal expression of SIRT1/HIF-1α in the PD model mice indicates that the SIRT1/HIF-1 signaling pathway may be involved in the development of PD.