Objective To investigate the association of dopamine D2 receptor with motor behavior and pathological characteristics of Parkinson's disease. Methods Wild type C57BL/6 mice (WT) and D2 receptor gene knockout mice (D2^-/-) were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce Parkinson's disease (PD) models. Pole test and swim test were used to observe the motor behaviors of mice. Immunofluorescence staining was used to observe tyrosine hydroxylase (TH)-positive neuron numbers in the substantia nigra of the midbrain. Results After MPTP injection, the animals had a significantly longer time in pole testing, a significantly decreased score in swimming test, and a significantly decreased number of TH-positive neurons in the substantia nigra of the midbrain(P<0.05 or P<0.01). Moreover, the behavioral changes and the decrease of TH-positive neuron numbers in D2^-/- mice were more significant than those in the WT mice(P<0.05 or P<0.01). Conclusion Dopamine D2 receptor plays an important role in motor behavior of PD mice, and lack of dopamine D2 receptor exacerbates the symptoms of MPTP-induced Parkinson's disease.