The potential impact of microplastics (MPs) on health has caused great concern, and a toxicology platform that realistically reproduces the system behaviour is urgently needed to further explore and validate MP-related health issues. Herein, we introduce an optically assisted thrombus platform to reveal the interaction of MPs with the vascular system. The risk of accumulation has also been evaluated using a mouse model, and the effect of MPs on the properties of the thrombus are validated via in vitro experiments. The microfluidic system is endothelialized, and the regional tissue injury-induced thrombosis is then realized through optical irradiation. Whole blood is perfused with MPs, and the invasion process visualized and recorded. The mouse model shows a cumulative risk in the blood with continuous exposure to MPs (P-value < 0.0001). The on-chip results show that MP invasion leads to decreased binding of fibrin to platelets (P-value < 0.0001), which is consistent with the results of the in vitro experiments, and shows a high risk of thrombus shedding in real blood flow compared with normal thrombus. This work provides a new method to further reveal MP-related health risks.