To investigate the effect of rosiglitazone on perihematomal brain tissue endothelin-1 (ET-1) expression and blood-brain barrier permeability in rabbits with intracerebral hemorrhage (ICH). Methods: Forty-five healthy rabbits were randomly divided into a normal control group (NC group), model control group (MC group), and rosiglitazone perfusion group (RSG group), with 15 rabbits per group. Autologous blood injection was used to establish basal ganglia ICH model. Six hours after generating model, rabbits in the RSG group were given a rosiglitazone perfusion to the lesion site. Each group was divided into three subgroups (5 rabbits per subgroup), and animals in each subgroup were euthanized on days 1, 3, and 7 post-procedure. Before euthanasia, neurological deficit scores (Purdy scores) were determined and Evans blue staining was performed to determine blood-brain barrier permeability. After rabbits were sacrificed, perihematomal brain tissue was removed to determine ET-1 expression. Data was analyzed for correlation between ET-1 expression levels and Evans blue stained perihematomal brain tissue and Purdy scores. Results: In MC and RSG groups, significant neurological impairment was found (P<0.05), and ET-1 expression and BBB permeability surrounding the lesion site were significantly increased compared to the NC group (P<0.05). When compared to the MC group, the RSG group showed a decrease in neurological impairment, ET-1 expression surrounding the lesion, and BBB permeability (P<0.05). ET-1 expression in perihematomal brain tissue showed significant correlation with blood-brain barrier permeability and Purdy neurological deficit scores (P<0.01). Conclusion: ET-1 expression in perihematomal brain tissue and blood-brain barrier permeability increased after intracerebral hemorrhage. RSG infusion therapy can reduce the expression of ET-1 in brain tissue around hematomas and decrease the permeability of the blood-brain barrier, thereby reducing neurological damage.