Ubiquitous　micro(nano)plastics　(MNPs)　are　emerging　environmental　pollutants,　which　pose　a　potential　threat　to　human　health.　When　MNPs　enter　the　blood　circulatory　system,　vascular　endothelium　is　one　of　the　most　important　target　organs　that　directly　interact　with　the　MNPs.　However,　little　is　known　about　the　cytotoxicity　of　MNPs　to　vascular　endothelial　cells.　In　this　study,　we　investigated　the　uptake　and　cytotoxic　effects　of　polystyrene　MNPs　with　a　particle　size　of　1 μm　(1-μm　PS-MNPs)　on　human　umbilical　vein　endothelial　cells　(HUVECs)　in　vitro.　Our　study　found　that　interaction　between　HUVECs　and　1-μm　PS-MNPs　was　at　a　very　low　level.　Even　at　the　high　exposure　concentration　of　25　μg/mL,　the　percentage　of　HUVECs　combined　with　fluorescent　1-μm　PS-MNPs　was　only　3.80%　using　flow　cytometry　analysis.　Moreover,　there　were　no　significant　differences　in　inflammation,　autophagy,　reactive　oxygen　species　(ROS)　level,　lactate　dehydrogenase　(LDH)　release,　and　adhesion　molecule　expression　following　exposure　to　1-μm　PS-MNPs　(5,　10,　and　25　μg/mL)　for　48　h,　except　for　a　remarkable　decrease　in　cell　viability　at　the　extremely　high　concentration　of　100　μg/mL.　Herein,　1-μm　PS-MNPs　showed　a　low　level　of　acute　toxicity　to　HUVECs　in　vitro,　and　we　expect　these　results　contribute　to　the　further　risk　assessment　of　MNPs　on　human　health.　©　2022　John　Wiley　&　Sons　Ltd.