Objectives: To observe the effects of minimally invasive surgery (MIS) for intracerebral hematoma (ICH) evacuation followed by rosiglitazone infusion therapy on peroxisome proliferator-activated receptor-gamma (PPAR gamma), blood-brain barrier (BBB) permeability, and neurological function. Methods: A total of 75 male rabbits (2.8-3.4 kg) were randomly assigned to a normal control group (NC group), a model control group (MC group), a rosiglitazone group (RSG group), a minimally invasive treatment group (MIS group) or a MIS combined with rosiglitazone group (MIS+RSG group). ICH was induced in all of the animals except for those in the NC group. The rosiglitazone was infused into the hematoma area in the RSG group and the MIS+RSG group. A MIS was performed to evacuate the ICH 6 h after the successful preparation of the ICH model in the MIS group and the MIS+RSG group. Each group included 15 rabbits and was divided equally into 3 subgroups (each subgroup included 5 rabbits that were killed on day 1, day 3, or day 7). Neurological deficit scores were determined, and the perihematomal brain tissue was removed to determine the PPAR gamma level and BBB permeability. Results: Neurological deficit scores, perihematomal PPAR gamma levels, and BBB permeability were all significantly increased in the MC group compared to the NC group. Performing the MIS alone to evacuate the ICH resulted in a marked decrease in these indices. The RSG used alone increased PPAR gamma levels and decreased BBB disruption. The MIS+RSG group displayed a marked increase in PPAR gamma levels and a more significant decrease in BBB permeability and neurological deficit scores. Conclusions: Performing MIS followed by PPAR gamma agonist infusion therapy is more efficacious for reducing secondary damage to the brain and improving neurological function.