Mangosteen peel extract is a xanthone group, that plays an important role in anti-angiogenesis. This study investigated mangosteen peel extract on cerebral neovascularization in type 2 diabetes mellitus (DM) rats. This study used 36 rats, randomized into six groups: C1 (negative control); C2 (high fat diet (HFD) and mangosteen peel extract at 200 mg/kg BW); C3 (HFD and diabetic); E1, E2, and E3 (HFD, diabetic, and extract at 100, 200, and 400 mg/kg BW respectively). All groups were measured body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR) and β cell function (HOMA-B), and histopathological feature of cerebral vascular (CV). There were significant differences in BMI, HOMA-IR, HOMA-B, and the mean number of CV (all p < 0.05) among treatment groups. E1-3 groups had a significantly lower level of blood glucose and HOMA-IR, and a higher level of HOMA-B and BMI (all p < 0.05) which tends to reduce cerebral neovascularization. HOMA-IR independently had a positive effect to induce neovascularization of CV (p < 0.05, R 2 = 26.8%). These findings suggested that mangosteen peel extract increased β-cell function sensitivity, and effectively suppressed insulin resistance, BMI, and cerebral neovascularization process in type 2 DM rats.