Objective: To investigate the effects of methamphetamine (Meth) on the protein expression of β-amyloid precursor protein（APP） and p-tau. Methods: Thirty C57BL/6J male mice were randomly divided into control group, saline treatment group and Meth treated group, then the mice were administrated intraperitoneally with 10 mg/kg Meth for 7 days and two times a day. The silver staining of Golgi apparatus was performed to investigate the number of neurons and the dendritic spines, and the pathological protein APP and p-tau were detected by western blot. Results: With the silver staining of Golgi apparatus, it showed that Meth significantly decreased the number of the neurons as well as the dendritic spines. With the Western blot assay, it suggested that Meth obviously up-regulated the pathological protein APP and p-tau expression in a dose- and time-dependent manner（P<0.05）. Intriguingly, pre-incubated with the neural cells with nifedipine, a blocker of the L-type Ca2+ channel, substantially attenuated Meth-mediated up-regulation of APP and p-tau. Conclusion: Meth exposure contributes Alzheimer's disease-like pathological changes, therefore, the present work will provide some supports for Meth-induced cognitive decline.