Lip redness is unique to humans and creates an important facial impression, but this redness decreases with age. Here, using histological and immunohistological staining of human upper lip vermilion from donors of different ages, we investigated blood vessels in the upper lip dermis and age-dependent histological changes. We found that both total vessel area in the dermis and vessel number in the upper dermis decreased with aging. Moreover, vessel number in the upper dermis correlated positively with development of rete ridges, which flattened with age, despite no significant change in the thickness of the stratified squamous epithelium. These findings suggest that age-related reductions in lip redness result from a decrease of blood vessels, which in turn leads to a flattening of the epithelium caused by the loss of rete ridges. This is the first study to histologically demonstrate age-related reductions in blood vessels in the lip. Our results provide an opportunity for enhancing blood flow/vascularization to improve the aesthetic appearance of the lips in the elderly.