Microplastic (MP) is plastic particle smaller than five millimeters. As an emerging environmental pollutant, they can potentially harm human health, but direct evidence of MP particles entering the circulating blood, lungs, and brain is limited. This study aimed to provide an overview of MP distribution and tissue damage following a single MP exposure in mice. We performed short-term uptake studies, administering 200-nm fluorescent MPs to mice by gavage at a dose of 200 mg/kg body weight. The MP fluorescence intensity in the blood was measured using fluorescence imaging 1, 2, and 4 h after gavage, finding it to peak after 2 h. The distribution and tissue damage 2 h after MP gavage were investigated. Fluorescence imaging detected the highest MP fluorescence intensity in the digestive system, particularly the stomach and cecum, followed by the lungs and spleen. Histological examination showed mild congestion in the liver and lungs and a small number of shed epithelium cells in the stomach and cecum. Light microscopy detected MP particles in the stomach, cecum, lungs, kidneys, liver, spleen, and brain, providing direct evidence that MP particles enter the blood circulation and translocate to other tissues. These results are vital to understanding MP' acute toxicity and potential effects.