Abstract: Objective To investigate the role of γ-secretase during the accumulation of β amyloid protein（ Aβ） induced by aluminum in rat’s brain. Methods A total of 32 male Sprague-Dawley（ SD） rats were randomly divided into control group,low,medium,and high dose group（ 0. 4 mg / kg BW,0. 8 mg / kg BW and 1. 2 mg / kg BW）. Aluminummaltolate exposure was conducted by intraperitoneal injection. Eight weeks later,Aβ and γ-secretase（ presenilin and nicastrin） were detected with enzym-linked immunosorbent assay（ ELISA） and western blot. Results Compared with the control group,the level of Aβ（ 120. 58 ± 23. 65 pg / ml） significantly increased in the cortex of high dose group（ P ＜0. 05）,and significantly increased in hippocampus of medium（ 115. 57 ±7. 00 pg/ml） and high dose group（ 127. 09 ± 11. 04pg / ml）（ P ＜ 0. 05）. There was no significant difference in the level of Aβ 40 in cortex and hippocampus of aluminum treated groups compared with that of the control group（ P ＞ 0. 05）. The level of Aβ 42（ 51. 02 ± 20. 90 pg / ml） significantly increased in cotex of high dose group,and in hippocampus of all the aluminum treated groups（ 24. 84 ± 5. 05, 42. 52 ± 12. 13,54. 42 ± 7. 98 pg / ml）. The expression of presenilin 1 and nicastrin increased significantly in cortex and hippocampus of medium and high dose group（ P ＜ 0. 05）. Conclusion The decreasing of of γ- secretase may be one of the reasons for aluminum-induced accumulation of Aβ.