Objective: To investigate the effects of Berberine on cerebral edema and neurological function in experimental intracerebral hemorrhage (ICH) rats and to explore the underlying mechanisms. Methods: Rats were randomly divided into five groups: sham group, ICH group, ICH rats treated with low, medium or high dose of Berberine group. ICH model was induced by injection of collagenase, and ICH rats were received Berberine by gavage once a day at dose of 10, 20 or 40 mg/kg, respectively. After 28-day treatment, the grade of neurological function was scored, the water content of brain was measured, the apoptotic cells in pre-hematoma area were detected with TUNEL staining, and the protein expression of Cleaved cas-3, Cleaved cas-9 and the release of cytochrome c from mitochondria to cytoplasm were determined by Western blot. Results: Compared with the ICH group, neurological function improved significantly and the brain water content decreased, as accompanied with the reduced number of apoptotic cells in pre-hematoma area. Moreover, the protein expression of Cleaved cas-3, Cleaved cas-9 and the release of cytochrome c from mitochondria to cytoplasm were dramatically inhibited after berberine treatment. Conclusion: Berberine protects against ICH-induced the impairment of neurological function through inhibition mitochondria-dependent intrinsic apoptosis pathway.