Epithelial barrier function is determined by both transcellular and paracellular permeability, the latter of which is mainly influenced by tight junctions (TJs) and apoptotic leaks within the epithelium. We investigated the protective effects of ferulate on epithelial barrier integrity by examining permeability, TJ protein expression, and apoptosis in Caco-2 cells treated withtert-butyl hydroperoxide (t-BHP), a strong reactive species inducer. Caco-2 cells pretreated with ferulate (5 or 15 μM) were exposed tot-BHP (100 μM), and ferulate suppressed thet-BHP-mediated increases in reactive species and epithelial permeability in Caco-2 cells. Moreover, ferulate inhibited epithelial cell leakage induced byt-BHP, which was accompanied by decreased expression of the TJ proteins zonula occludens-1 and occludin. In addition, pretreatment with ferulate markedly protected cells againstt-BHP-induced apoptosis, as evidenced by decreased nuclear condensation, cytochrome c release, and caspase-3 cleavage and an increased Bax/Bcl-2 ratio. These results suggest that ferulate protects the epithelial barrier of Caco-2 cells against oxidative stress, which results in increased epithelial permeability, decreased TJ protein expression, and increased apoptosis. The most significant finding of our study is the demonstration of protective, ferulate-mediated antioxidant effects on barrier integrity, with a particular focus on intracellular molecular mechanisms.