Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury, but it remains unclear whether melatonin can also ameliorate cerebral microvascular abnormalities. Rat models of Alzheimer\'s disease were established by six intracerebroventricular injections of amyloid-beta 1–42, administered once every other day. Melatonin (30 mg/kg) was intraperitoneally administered for 13 successive days, with the first dose given 24 hours prior to the first administration of amyloid-beta 1–42. Melatonin ameliorated learning and memory impairments in the Morris water maze test, improved the morphology of microvessels in the cerebral cortex and hippocampus, increased microvessel density, alleviated pathological injuries of cerebral neurons, and decreased the expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2. These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors, thereby improving the cognitive function of patients with Alzheimer\'s disease. This study was approved by the Animal Care and Use Committee of Jinzhou Medical University, China (approval No. 2019015) on December 6, 2018.