BACKGROUND: Considering widely administration of methylphenidate and also its immunosuppressive effects on different organs, importance of related microscopic studies is obvious. OBJECTIVES: Determining histological effects of methylphenidate on adrenal glands and lymphatic organs in mice. METHODS: A total number of 30 adult male Balb/C mice were provided, weighed and divided into one control and two experimental groups. The control group received water by gavages once a day, for 40 days. The experimental groups were orally administered MPH hydrochloride (2mg/kg and 10mg/kg body weight,) respectively. Animals were anesthetized and blood samples were collected through cardiac puncture for analysis of blood cells. Spleen, thymus, lymph nodes and adrenal glands were removed and processed for microscopic studies through hematoxylin and eosin staining. Spleen samples were processed for plasma cell count and staining (label antibody CD138*). The data were analyzed using analysis of variance (ANOVA) and p