Objective To compare the difference of spatial reference memory and dopamine (DA) level in the brain between acute,subacute and chronic mouse model of Parkinson' s disease(PD) induced by 1-methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine(MPTP) injection. Methods The acute,subacute and chronic mouse model of Parkinson' s disease were induced by injecting the same MPTP volume dose with different schedules. The spatial reference memory of mice was tested by morris water maze. Dopamine concentration in striatum, hippocampus and the prefrontal cortex were detected with HPLC. The number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry. Results The mean escape latency of the chronic but not the acute or subacute mouse model of Parkinson' s disease was significant longer ( P ＜ 0.05 ) than its control group. The striatum DA concentration of three test groups ( ( 1180. 1 ± 293.0 ) ng/ml, ( 1177.4 ± 450.5 ) ng/ml,( 1149.6 ± 353.0 ) ng/ml ) reduced significantly compared to their control groups ( ( 225.6 ± 79.7 ) ng/ml, ( 273.6± 64.9 ) ng/ml, ( 327. 1 ± 126.2 ) ng/ml, P ＜ 0.01 ). The prefrontal cortex DA concentration of the acute mouse model of Parkinson' s disease ( ( 65.3 ± 23.9 ) ng/ml ) was significant lower than its control group ( ( 41.2 ±18.8 )ng/ml, P ＜ 0.05 ). No significant changes of hippocampus DA concentration were seen between these test groups and their control groups. The number of TH positive cells in substantia nigra significantly decreased in three test groups compared to their control groups( P ＜ 0.05 ). Conclusion The difference of spatial reference memory between three regimens of the mouse model of Parkinson' s disease may not due to the difference of DA level in their brain.