ABSTRACTThe increasing prevalence of microplastics pollution is a significant environmental challenge. However, the effects of these particles on learning and memory remain poorly understood. The aim of this investigation was to ascertain the influence of miR‐532‐5p on cognitive and memory deficits induced by polystyrene microplastics (PS‐MPs) and to identify the underlying mechanisms. PS‐MPs were administrated orally to male rats at a dose of 30 mg/kg for 8 weeks. In the treatment group, miR‐532‐5p was injected intracerebroventricularly (ICV) at a dose of 2.5 μg/2.5 μL. To assess the effects of PS‐MPs exposure on learning and memory functions, the novel object discrimination (NOD), Y‐maze, and Barnes maze tests were used, which showed a detrimental effect on the subjects' learning and memory abilities. In the hippocampal tissue of the rats exposed to PS‐MPs, the levels of MDA, protein carbonyl, nitrite, TNFα, NLRP3, Caspase 1, caspase 3, and GFAP were increased, and levels of SOD, catalase, SIRT1, and BDNF were decreased. In addition, exposure to PS‐MPs increased AChE activity, activated the PERK/GRP78/CHOP signaling pathway, and inactivated the Wnt/β‐catenin and PI3K/Akt signaling pathways. Conversely, ICV injection of miR‐532‐5p led to a reversal of the hippocampal levels of all aforementioned factors. Therefore, exposure to PS‐MPs can affect learning and memory functions by inducing oxidative stress, neuroinflammation, apoptosis, pyroptosis, and ER stress, and treatment with miR‐532‐5p can restore learning and memory through its anti‐inflammatory, antioxidant, and anti‐pyroptosis properties.