Objective To explore the effect of amphetamine on eukaryotic translation elongation factor 2 (eEF2) in the frontal cortex of mice.Methods Male C57BL/6 mice were randomly divided into normal control group (n=10),saline group (n=10) and amphetamine treatment group (n=40);the amphetamine treatment group was divided into 1,7,14 and 28 d subgroups (n=10).Mice in the amphetamine treatment group were treated with amphetamine 2 mg/(kg· d) via intraperitoneal injection;those in the saline group received a same dose of saline,while those in the normal control group received no treatment.Autonomous behavior activities were tested during establishing amphetamine models.Immunohistochemistry and Westem blotting were used to identify the eEF2 expressions.Results Behaviour test showed that total moving distance,average speed,maximum speed,moving fast time/total time in the 7,14 and 28 d amphetamine treatment subgroups were significantly increased as compared with those in the normal control group and saline group (P＜0.05).Immumohistochemical staining indicated that the grey values of eEF2-positive inummoreactive products in the amphetamine treatment group were significantly lower than those in the normal control group and saline group (P＜0.05);those of eEF2-positive inummoreactive products in 14 and 28 d amphetamine treatment subgroups were significantly lower than those in 1 and 7 d amphetamine treatment subgroups (P＜0.05).Western blotting showed that eEF2 protein expression in the frontal cortex was significantly elevated in the amphetamine treatment group as compared with that in the other two groups (P＜0.05);the eEF2 expression in the amphetamine treatment group increased with time prolonging within 28 days after establishment of models.Conclusion Amphetamine can induce increased eEF2 expression in the frontal cortex of mice.