Objective To investigate the expression of cytochrome C in perihematomal brain tissue and its relationship with the histopathological change and formation of cerebral edema in patients with hypertensive cerebral hemorrhage. Methods Thirty four patients (23 male, 11 female) of hypertensive cerebral hemorrhage in hospital from Sep. 2001 to Sep. 2002 were selected with a mean age 55.6± 10.2 years (from 35 to 75 years). The mean volume of hemorrhagic blood was 50.4±11.6 ml (from 25 to 85 ml). The perihematomal brain tissue was obtained from the minimally invasive surgery. Histopathological change and expressions of cytochrome C in perihematomal brain tissue was detected by histopathological and immunohistochemical techniques. The volume of perihematomal cerebral edema was determined by computed tomographic scan before operation. The results of staining and the volume of perihematomal cerebral edema were analyzed with double blind fashion. Results Perihematomal cerebral edema were found 12-72h after cerebral hemorrhage. Myelin sheath degeneration, condensation of nucleus and typical apopototic body were observed in perihematomal brain tissue. Expression of cytochrome C in perihematomal brain tissue was observed at 4 h and reached peak around 48-72 h after cerebral hemorrhage. Cytochrome C expressed higher positively in 16 patients and lower positively in 13 patients. Cytochrome C expression was not detected only in 5 patints. There were significant differences in volume of perihematomal cerebral edema with different expression of cytochrome C in perihematomal brain tissue (P＜0.01). Conclusions Cytochrome C expression was upregulated in perihematomal brain tissue in patients with hypertensive cerebral hemorrhage. Cytochrome C might involve in the histopathological change and the formation of perihematomal cerebral edema.