Abstract: Objective: To investegate the effect of phosphorylated-P38MAPK(mitogen-activated protein kinase) on the expression of caspase-3 in the substania nigra（SN）of MPTP-induced mouse model of（PD）. Methords: Mice were randomly divided into MPTP model group, which were treated with MPTP(30 mg/kg, dissolved in saline, intraperitoneal injection), inhibitor group, which were treated with SB203580(10 mg/kg, dissolved in 5 mg/ml DMSO, intraperitoneal injection) 1 h before injection of MPTP. Once a day for 5 days; control group were treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and western blot for TH, caspase-3 and phosphorylation of P38MAPK were used to observe the change of positive cell number numbers and the expression level in the SN of midbrain. Results: Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respectively（P<0.01）, the numbers of caspase-3 and phosphorylation of P38MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly（P<0.01). After giving SB203580, the above changes were reduced obviously（P<0.01）. Conclusions: In the mouse model of subacute Parkinson's disease induced by MPTP, phosphorylated-P38MAPK regulated caspase-3 in the SN of midbrain, the specific P38MAPK inhibitor SB203580 is neuroprotective to the mouse model.