To investigate the effect of minimally invasive surgery for hematoma evacuation combined with metformin on the perilesional inflammatory response after intracerebral hemorrhage (ICH) in rabbits. Methods: Sixty male rabbits were randomly divided into 5 groups: the normal control (NC), model control (MC), metformin (MET), minimally invasive surgery (MIS), and minimally invasive surgery combined with metformin (MIS+MET) groups. Six hours after establishing the ICH model, sham hematoma evacuation was performed on the MC group and MET group rabbits, and minimally invasive evacuation surgery was performed on the MIS group and MIS +MET group rabbits. After surgery, metformin was administered by gavage to MET group and MET +MIS group, while saline was given to the other groups. On the 3rd and 7th day after surgery, Purdy scores were obtained and the rabbits were sacrificed. Perihematomal brain tissue was obtained to deter- mine water content, and the expression levels of TNF-α, IL-1β, and Iba-1 were detected by immunohistochemical staining. Results: Compared with the MC group, the Purdy score, brain tissue water content, and expression of TNF-α, IL-1β, and Iba-1 in the MIS, MET, and MET+MIS groups were significantly decreased (P<0.05), and the change in the MIS+MET group was most apparent. Conclusion: The combination of minimally invasive surgery and metformin can reduce the nerve injury, cerebral edema, and perihematomal expression of TNF-α, IL-1β, and Iba-1 after ICH in rabbits.