Objective: To investigate the protective effects and the possible mechanisms of Senegenin on hippocampal neurons in rats with acute intracerebral hemorrhage (ICH). Methods: Rats were randomly divided into a sham group, a model group, a low dose Senegenin treatment group and a high dose Senegenin treatment group. ICH rat model was established by injection of autologous blood, and ICH rats were administrated with 6 or 12 mg/kg of Senegenin. The impairment of neural function was scored. The water content of brain was measured. The cell size and cell-packing density of hippocampal CA1 region around the hematoma were determined by Nissl’s staining. The apoptosis of hippocampal CA1 region tissue around the hematoma was analyzed by TUNEL staining. The protein expressions of Bax, Bcl-2 TGF-β1 and VEGF of hippocampal CA1 region tissue around the hematoma were detected by Western blot. Results: Compared with the model group, the scores of neural function impairment were significantly decreased and the brain water content after the treatment with low or high dose of Senegenin were decreased, cell apoptosis of hippocampal CA1 region around the hematoma was inhibited, cell-packing density of hippocampal CA1 region around the hematoma was reduced, cell size of hippocampal CA1 region around the hematoma was increased. Furthermore, the protein expression of Bax was obviously decreased, whereas Bcl-2 TGF-β1 and VEGF protein expression were increased in hippocampal CA1 region around the hematoma. Conclusion: Senegenin improves neural function in ICH rats, which may be associated with reducing cerebral edema and regulation of Bax, Bcl-2 TGF-β1 and VEGF protein expression.