Abstract： Background Hypertensive intracerebral hemorrhage (HICH) is a severe disease with high morbidity and mortality.Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries.However, there has long been a debate over the proper timing of such surgery.In this study, we explored the optimal operation time for HICH patients by observing the pathological changes in perihematomal brain regions during different stages of onset.Methods Twenty-five specimens of brain tissue, obtained from perihematomal region of HICH patients in different phases, were subjected to haematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) staining and Caspase-3, matrix metalloproteinases-9 (MMP-9)immunohistochemical staining.The changing roles of necrosis and apoptosis and the expression of MMP-9 and Caspase-3 positive cells were all observed using image analysis.Results The obvious expression of TUNEL positive cells was recognized within 6 hours of ICH onset, reaching its peak between 6 hours and 24 hours in the early phase.Results were highly consistent with Caspase-3 and MMP-9 positive cell counts.Necrosis was found 6 hours after ICH onset and aggravated after 12 hours.Conclusions In the early phase, apoptosis was seen as a major modality of injury in the brain tissue of the perihematomal region and was strongly correlated with the expression of MMP-9 and Caspase-3.The results of the present study suggest that an operation performed as soon as possible after iCH onset may be optimal for preserving the nervous system function.