Multiple microRNAs (miRNAs) have been found to be linked with cerebral ischemia. Thus, this study was employed to characterize the capabilities of miRNA-103a (miR-103a) on the brain microvascular endothelial cells (BMECs) injury in rat models of middle cerebral artery occlusion (MCAO) by regulating AXIN2. The MCAO rat model was developed by the suture method, where normal saline, miR-103a inhibitors, or its negative control were separately injected into the lateral ventricle to assess the function of miR-103a inhibitors in BMECs apoptosis, microvessel density, as well as angiogenesis. In addition, the oxygen-glucose deprivation model was induced in primarily cultured BMECs to unearth the functions of miR-103a inhibitors on cell viability and apoptosis, lactate dehydrogenase (LDH) release and tube formation ability. Furthermore, the relationship between miR-103a and AXIN2 was verified. The modeled rats of MCAO showed robustly expressed miR-103a, poorly expressed AXIN2, severe neurological deficits, accelerated apoptosis and reduced angiogenesis. miR-103a expression had a negative correlation with AXIN2 messenger RNA expression (r = -0.799; p < .05). In response to the treatment of miR-103a inhibitors, the BMECs apoptosis was suppressed and angiogenesis was restored, corresponding to upregulated Bcl-2, VEGF, and Ang-1, in addition to downregulated caspase-3 and Bax. Meanwhile, AXIN2 was verified to be the miR-103a's target gene. More important, miR-103a inhibitors led to promoted BMEC viability and tube formation and suppressed apoptosis and LDH release rate. This study highlights that miR-103a targets and negatively regulates AXIN2, whereby reducing BMEC injury in cerebral ischemia. © 2019 Wiley Periodicals, Inc.