This study investigates the cardiovascular toxicity of polystyrene microplastics (PS-MPs) in rats using untargeted metabolomics analysis. Forty-eight 6-week-old Wistar rats were divided into four groups and exposed to different concentrations of PS-MPs (0, 0.5, 5, and 50 mg/kg/day) via intragastric administration for 90 days. Following exposure, biochemical markers in myocardium, aorta, and blood were analyzed, and HE staining was performed to assess the toxic effects of PS-MPs on the cardiovascular system. Additionally, non-targeted metabolomics was used to analyze the effects of PS-MPs exposure on cardiovascular metabolism in rats and to explore potential molecular mechanisms. The results showed no significant pathological changes in the heart and aorta following PS-MPs exposure. However, the myocardial enzyme levels in the high-dose group showed a significant increase. PS-MPs exposure caused lipid metabolism disorders in rats, leading to increased inflammation and oxidative stress indicators in myocardial and aortic tissues, but decreased IL-6 levels. Untargeted metabolomics results showed that metabolites with antioxidant and anti-inflammatory effects, including equol and 4-hydroxybenzoic acid, were significantly upregulated. The study found that long-term exposure to high concentrations of PS-MPs may lead to abnormal lipid metabolism and cardiovascular system damage, with mechanisms possibly involving oxidative stress and inflammatory responses. Exogenous antioxidants and changes in own metabolites may have a protective effect on the injury. The findings suggest that PS-MPs may induce local inflammation and oxidative stress, leading to organ damage through mechanisms such as disrupting cell morphology and affecting cell energy metabolism. The study provides new insights into the cardiovascular toxicity of PS-MPs and its prevention and treatment.This study investigates the cardiovascular toxicity of polystyrene microplastics (PS-MPs) in rats using untargeted metabolomics analysis. Forty-eight 6-week-old Wistar rats were divided into four groups and exposed to different concentrations of PS-MPs (0, 0.5, 5, and 50 mg/kg/day) via intragastric administration for 90 days. Following exposure, biochemical markers in myocardium, aorta, and blood were analyzed, and HE staining was performed to assess the toxic effects of PS-MPs on the cardiovascular system. Additionally, non-targeted metabolomics was used to analyze the effects of PS-MPs exposure on cardiovascular metabolism in rats and to explore potential molecular mechanisms. The results showed no significant pathological changes in the heart and aorta following PS-MPs exposure. However, the myocardial enzyme levels in the high-dose group showed a significant increase. PS-MPs exposure caused lipid metabolism disorders in rats, leading to increased inflammation and oxidative stress indicators in myocardial and aortic tissues, but decreased IL-6 levels. Untargeted metabolomics results showed that metabolites with antioxidant and anti-inflammatory effects, including equol and 4-hydroxybenzoic acid, were significantly upregulated. The study found that long-term exposure to high concentrations of PS-MPs may lead to abnormal lipid metabolism and cardiovascular system damage, with mechanisms possibly involving oxidative stress and inflammatory responses. Exogenous antioxidants and changes in own metabolites may have a protective effect on the injury. The findings suggest that PS-MPs may induce local inflammation and oxidative stress, leading to organ damage through mechanisms such as disrupting cell morphology and affecting cell energy metabolism. The study provides new insights into the cardiovascular toxicity of PS-MPs and its prevention and treatment.