Objective: To observe the effect of intra-hematoma Rosiglitazone (RSG) infusion therapy in treating intracerebral hemorrhage (ICH). Specifically, to explore the effects of RSG on tight junction associated proteins Occludin and ZO-1 expression within perihematomal brain tissues as well as the blood-brain barrier (BBB) permeability after ICH in rabbits.Methods: A total of 30 rabbits were randomly assigned to three groups including sham control group (NC group, n = 10), hemorrhage model group (HM group, n = 10), and hemorrhage model with RSG treatment group (RSG group, n = 10). ICH was induced in rabbits of HM group and RSG group, involving an injection of autologous non-anticoagulant artery blood (0.3 mL, similar to basal ganglia hematoma 30 mL in humans) into the left basal ganglia of the rabbits' brains. The NC group was injected with the same amount of saline into the same area. Six hours later after ICH induction or sham surgery, the RSG group received the intra-hematoma RSG (0.5 mg/0.1 mL) infusion, meanwhile the NC group and the HM group were injected with saline (0.1 mL) into the hematoma area. On day seven, the perihematomal brain tissues were obtained to determine the Occludin and ZO-1 expressions by Western Blot and RT-PCR, and the BBB permeability by the Evan' s Blue (EB) content.Results: Occludin and ZO-1 expressions and mRNA levels were all significantly decreased in the HM group and RSG group compared with the NC group (P < 0.01). Occludin and ZO-1 expressions and mRNA levels were all significantly increased in the RSG group compared with the HM group (P < 0.01). The EB contents were all significantly increased in the HM group and RSG group compared with the NC group (P < 0.01). The EB content was significantly decreased in the RSG group compared with the HM group (P < 0.01).Conclusion: Intra-hematoma RSG infusion therapy could increase the expressions of tight junction associated proteins Occludin and ZO-1 in the perihematomal brain tissues and decrease the BBB permeability in rabbits after ICH.(c) 2023 International Hemorrhagic Stroke Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).