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Background: Microplastics (MPs) and Nanoplastics (NPs) are plastic fragments that spread in the environment and accumulate in the human body, so they have been becoming a worldwide environmental concern because of their potential human health effects. The aim of this systematic review was to investigate the prospective impact of MPs and NPs on the inflammatory process. Methods: Electronic article search was performed on PubMed, Scopus and Web of Science international databases from 1 Jan 2012 to 31 Dec 2021. Screenings of titles, abstracts and full texts were performed according to the Preferred Reporting Item for Systematic Review and Meta-analyses (PRISMA). The methodological quality of the studies was checked by the Toxicological data Reliability Assessment Tool. Results: Electronic article search identified 125 records, from which 6 in vitro, 11 in vivo and 2 both in vivo and in vitro studies were included. Both in vivo and in vitro studies have showed an increase ofdifferent inflammatory outcomes (Interleukines, Tumor necrosis factor, Chemokines, Interferones, Transcription factors, Growth factors, Oxydoreductase, Proteins and others), thus it seems to confirm the association withthe exposure to microplastics of different types, sizes, exposure times and exposed species. Conclusions: This systematic review seems to support the relationship between the exposure to MPs and the inflammatory processboth in vivo and in vitro. Greater caution is needed about the role of NPs because ofa very small number of studies. Additional high-quality studies are warranted to confirm these results, especially the research should be focused on NPs being lacking literature.