One of the major impediments in tissue-engineered oral mucosa (TEOM) is the lack of rete ridge (RR) structures that can weaken the connection between the epidermis and dermis. This study aimed to investigate the native morphology of RRs as well as the expression of extracellular signal-regulated kinase 1/2 (ERK1/2), Ki67, and keratin-19, which are related to cell mechanotransduction, proliferation, and stemness in the oral epidermis, respectively. RR characteristics, including type, density, length, and width, were analyzed in the masticatory mucosa (Mm) and lining mucosa (Lm) sites of 52 specimens. The expression of ERK1/2, Ki67, and keratin-19 was assessed by immunohistochemistry. ERK1/2 activation by masticatory stimuli was confirmed in vitro by loading pressure onto cultured keratinocytes isolated from the specimens. Three types of RR were found. The RRs in the Mm and Lm differed. The length and percentage of ERK1/2-positive (%ERK1/2+) basal layer cells had a negative correlation (p = 0.004), whereas the length and %Ki67+ basal layer cells had a positive correlation (p = 0.013). The %ERK1/2+ basal layer cells and %keratin-19+ basal layer cells had a negative relationship (p = 0.011). ERK1/2 activation in the oral epithelium was induced by pressure and propagated in cultured keratinocytes. RRs are longer in the Mm, which may result from the topical basal cell proliferation and migration induced by masticatory pressure via ERK1/2 activation. Our findings preliminarily interpret RR histomorphology as influenced by oral masticatory pressure. Results may benefit future studies on RR development and reconstruction in TEOM models to enhance the epidermis-dermis connection. Copyright © 2012 S. Karger AG, Basel.