OBJECTIVE: To observe effects of rosiglitazone (RSG) infusion therapy on perihematomal peroxisome-proliferator-activated receptor gamma (PPAR gamma), glutamate, blood-brain barrier (BBB) permeability, and brain edema. METHODS: Fifty male rabbits (2.8-3.4 kg) were randomly assigned to a normal control (NC) group, model control (MC) group, RSG group, minimally invasive surgery (MIS) group, or MIS and RSG (MIS+RSG) group. Intracranial hemorrhage was induced in all rabbits except for the NC group. MIS procedures were performed to evacuate the intracranial hemorrhage 6 hours after the intracranial hemorrhage model was prepared successfully. The animals were sacrificed on day 7, and the perihematomal brain tissue was obtained to determine PPAR gamma, glutamate, and BBB permeability. RESULTS: Compared with the MC group, the MIS group displayed a remarkable decrease in PPAR gamma, glutamate, and BBB permeability. The RSG group showed similar results in glutamate level and BBB permeability but a significant increase in PPAR gamma. The MIS+RSG group displayed an increase in PPAR gamma and a more significant decrease in glutamate, BBB permeability, and neurologicl deficit scores compared with the other groups. CONCLUSIONS: Performing MIS followed by RSG infusion therapy might increase PPAR gamma expression and might be more efficacious for reducing glutamate level and BBB permeability and improving neurologic function than MIS or RSG therapy used alone.