Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder with a serious negative impact on the quality of life from childhood until adulthood, which may cause academic failure, family disharmony and even social unrest. The pathogenesis of ADHD has remained to be fully elucidated, leading to difficulties in the treatment of this disease. Genetic and environmental factors contribute to the risk of ADHD development. Certain studies indicated that ADHD has high comorbidity with allergic and autoimmune diseases, with various patients with ADHD having a high inflammatory status. Increasing evidence indicated that mast cells (MCs) are involved in the pathogenesis of brain inflammation and neuropsychiatric disorders. MCs may cause or aggravate neuroinflammation via the selective release of inflammatory factors, interaction with glial cells and neurons, activation of the hypothalamic-pituitary adrenal axis or disruption of the blood-brain barrier integrity. In the present review, the notion that MC activation may be involved in the occurrence and development of ADHD through a number of ways is discussed based on previously published studies. The association between MCs and ADHD appears to lack sufficient evidence at present and this hypothesis is considered to be worthy of further study, providing a novel perspective for the treatment of ADHD.