In the present study, we tested the effect of cold water stress (CWS) on dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model, and found that CWS pretreatment elicited less MPTP neurotoxicity. To understand the molecular mechanism underlying this phenomenon, we detected the expression of heat shock protein 70 (Hsp70) in the striatum of the experimental mice, and found that CWS pretreatment could significantly increase striatal Hsp70 in MPTP-treated mice. Furthermore, in parallel with the induction of Hsp70, the MPTP-induced increase of striatal α-synuclein was inhibited in the CWS + MPTP-treated mice. CWS pretreatment also significantly inhibited the reduction of anti-apoptotic molecule Bcl-2 expression in the striatum and enhanced Bcl-2 transcription in the substantia nigra of MPTP-treated mice. Taken together, these data indicated that Hsp70 might be an important intermediate for the neuroprotective effect of CWS against MPTP-induced dopaminergic toxicity.