Microplastics (MPs) are ubiquitous contaminants in the environment and can be transferred along the food chain, thus causing adverse effects in organisms, even human beings. Therefore, it is of practical importance to identify the environmental risks of MPs, which could lead to a significant impact on public health. In addition to the healthy population, there are large numbers of patients with chronic diseases around the world whose responses to MPs are understudied, representing a significant knowledge gap within the health risk assessment of MPs. In this study, the response sensitivity to MPs of mice with acute colitis was compared with that of healthy mice. The mice were fed water containing polystyrene microplastics (PS MP) at a concentration of 500 μg/L for 28 days. The results showed that PS MP exposure induced inflammatory effects and exerted great disturbance on liver metabolites. Moreover, exposure to PS MP exaggerated dextran sodium sulfate (DSS)-induced acute colitis, as well as lipid disorders, as verified by typical inflammatory factor expression and triglyceride accumulation. The increased intestinal permeability of mice with acute colitis caused by exposure to PS MP may be responsible for the upregulated adverse effects. The results of this study suggest that populations with chronic diseases might be more sensitive to environmental contamination, which should be considered during health risk assessments.