Updated project metadata. Tenuigenin (TNG), an extract obtained from Polygalae Radix, possesses anti-inflammatory,anti-oxidant, neuro-protective properties. However, the potential mechanism of TNG on intracerebral hemorrhage (ICH) has not been well studied. Therefore, in this study, we aimed to identify the prospective mechanism of TNG in treating ICH with the help of TMT-based quantitative proteomics. Our results showed that the optimal dose of TNG was 16mg/kg, which could markedly improve neurological functions, reduce cerebral edema, hematoma volume and hemoglobin level 72h after ICH. Furthermore,our proteomic results identified that a total of 404 DEPs (353 up and 51 down regulated) were identified in ICH+vehicle vs Sham group, while 342 DEPs (306 up and 36 down regulated) and 76 DEPs (28 up and 48 down regulated) were quantified in TNG vs Sham group and TNG vs ICH+vehicle group respectively. In addition, a total of 26 DEPs were selected out according to strict criteria. Complement and coagulation cascades was the most significantly enriched pathway and two proteins (MBL-C and Car1) were further validated as hub molecules.