Objectives: Peritoneal fibrosis is one of the major hurdles limiting the long-term maintenance of peritoneal dialysis. Microplastics have recently emerged as an important environmental concern. In this study, we investigated the effects of microplastics on human peritoneal mesothelial cells (HPMCs). Methods: Human peritoneal mesothelial cells were exposed to microplastics (1.0 or 10 μM) for 24 hours. Markers of epithelial-to-mesenchymal transition (EMT), cellular senescence, oxidative stress, and the senescence-associated secretory phenotype (SASP) were evaluated using immunofluorescence staining, western blotting, RT-PCR, and reactive oxygen species (ROS) assays. Results: Exposure to microplastics did not significantly affect cell viability; however, it induced morphological changes of HPMCs to a spindle-shaped phenotype, suggesting the induction of EMT. Western blot analysis demonstrated increased expression of fibrotic markers, including α-smooth muscle actin and fibronectin, along with increased expression of senescence-related markers such as p53 and decreased expression of epithelial cell markers. Senescence-associated β-galactosidase activity also showed an increasing trend following microplastic exposure. In addition, markers related to oxidative stress and DNA damage, including DSB and DCF-DA fluorescence, were increased in microplastic-treated cells. Conclusion: Microplastic exposure may induce oxidative stress in human peritoneal mesothelial cells, leading to cellular senescence and epithelial-to-mesenchymal transition, which may ultimately contribute to the development of peritoneal fibrosis.