Ingested microplastics (MPs) can accumulate throughout whole body, which may induce the dysfunction of immune system. However, it remains unclear how MP exposure affects innate immune responses at the cellular level. We found that mouse neutrophils strongly bind and then engulf polystyrene MPs. This interaction leads to proinflammatory state of neutrophils and eventually results in apoptotic cell death through toll-like receptor signaling pathway in a bacteria-recognition mimetic manner. Moreover, our data verified that orally administered polystyrene MPs reach various organs in mice, where they are interacted with and endocytosed by neutrophils. We confirmed that human neutrophils also strongly bind and internalize polystyrene MPs. Additionally, RNA sequencing analysis of polystyrene MPs-exposed human neutrophils showed the upregulation of cell death-related function. Therefore, the accumulated MPs may exacerbate inflammatory immune response by disrupting neutrophil function. These results provide novel insight into the adverse responses of neutrophils induced by MP exposure.