Introduction: Methamphetamine is a central nervous system stimulant and one of the most common drugs which used in the United States and some Asian countries like Japan. Its use has been increased in the recent years in Iran. Using histological and stereological methods the aim of this study was to investigate the effects of long-term administration of methamphetamine on the number and size of different cell layers of the cerebellum in mice. Materials and Methods: A total of 30 male mice (weight: 45gr, age: 8 weeks) were divided into three groups (10 mice each group) and group I (control) received normal saline and groups II and III received methamphetamine (0.1 and 1 mg/kg respectively), intra-peritoneally. The animals were anesthetized with ketamine after one month and the cerebellum was removed and fixed in 5% formalin. Then, the left cerebellum hemispheres slides were stained with toluidine blue and hematoxylin-eosine method. The volume of cerebellar cortex layers was investigated by Cavalieri's principle, using point counting. To calculate the number of Purkinje and granular cells, physical dissector method was used. Results: Methamphetamine decreased cerebellar volume, the volume of the granular layer, the number of granular and Purkinje cells in both experimental groups compared to control group. Methamphetamine consumption also decreased the volume of molecular layer in the 1 mg/kg group compared to control group. Furthermore, methamphetamine increased the volume of white matter in the 1 mg/kg group compared to control mice and the 0.1 mg/kg group. Conclusion: Methamphetamine reduces the cells and volume of cerebellar possibly due to cell injury and neuronal death. Enhancement of the white matter could be a compensatory reaction to the cerebellum cells loss.