Objective The aim of this study was to establish a mouse model of chronic Parkinson's disease induced by systemic administration of lipopolysaccharide plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP), and to study the changes of behavioral manifestation, numbers of dopaminergic neurons in the substantia nigra pars compacta. Methods Twenty C57BL mice were randomly divided into 2 groups: the saline control group and model group. The mice in the model group received three intraperitoneal (i.p.) injections of LPS (0.25 mg/kg), once daily for three consecutive days. Four hours following the final LPS injection, the mice received one subcutaneous injection of low-dose MPTP (25 mg/kg). The mice of control group were injected with the same volume of saline. Eight weeks later, the motor ability of the mice was evaluated by footprint test and rotarod test. The tyrosine hydroxylase (TH)-positive cells were observed by immunohistochemical analysis. Results Compared with the control group, the scores of behavioral test were significantly lower, numbers of TH immunoreactive cells were significantly less in the Parkinson's model group (P<0.05). Conclusions Behavioral manifestation,number of dopaminergic neurons in the substantia nigra are significantly changed in the mouse models of Parkinson's disease produced by repeated injection of LPS plus MPTP, suggesting that this chronic animal model can be used in the experimental study for pathogenesis and therapy of Parkinson's disease.