Abstract: Objective:To study the acute and long-term toxicity of grape seed proanthocyanidin extract (GSPE) , in order to provide safety experimental proof for clinical application. Methods:In the acute toxicity study, mice were intragastrically administered with GSPE in different concentrations, and calculate the median lethal dose (LD50) by Bliss method. In the long-term toxicity study, rats were randomly divided into four groups:blank control group, maximum (428.57mg/ (kg·d) ) , middle (214.29mg/ (kg·d) ) , minimum (42.86mg/ (kg·d) ) dose group of GSPE. After continuously took GSPE orally for 26 weeks, rats behavior, weight gain, food consumption, blood test, biochemistry test, urine test, systematic autopsy and histopathologic diagnosis were observed. These above indexes were inspected again 4 weeks after cease of feeding. Results:The oral acute toxicity study of GSPE in mice revealed that the LD50 was 3451.9mg/kg. The long-term toxicity study showed that no significant differences were observed in rat's behaviors, food intake and relative examination indexes among the 3 different dosage groups of GSPE, which compared with normal control group. There was no abnormal result of blood test, biochemistry test, urine test and histopathologic diagnosis in rats. Conclusion:These studies demonstrated that GSPE was safe and did not cause any detrimental effects in vivo under these conditions in this study.