Objective: To establish a Parkinson's disease (PD) cell model of human neuroblastoma cells (SH-SY5Y) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to explore the possible mechanism of trehalose in PD. Methods: SH-SY5Y cells were cultured and divided into four groups: control group, trehalose group, MPTP group and trehalose +MPTP group.The trehalose was detected with MTT assay for its effect of on the viability of injured SH-SY5Y cells. The lactate dehydrogenase (LDH) was detected by kit for its level in culture medium. The ROS was assessed by DCFH-DA for its average level in cells. Besides, Hoechst 33342 staining was used to detect apoptosis. The endoplasmic reticulum stress (ERS) related proteins GRP78, IRE1, PERK and ATF6 were also detected by Western blot for its expression levels. Results: The survival rate of MPTP group decreased significantly and the levels of LDH and ROS increased compared with the control group. In addition, the survival rate of cells in trehalose +MPTP group increased significantly and the levels of LDH and ROS decreased compared with MPTP group. The expressions of GRP78, IRE1, p- IRE1, PERK, p- PERK and ATF6 in MPTP group increased, but decreased in trehalose +MPTP group compared with the control group. Conclusion: Trehalose has a significant protective effect on MPTP-induced SH-SY5Y cells injury, and its mechanism may be related to the effect of trehalose on oxidative stress by inhibiting ER stress response.