Syringic acid (SA) is an abundant phenolic acid compound that has been demonstrated to yield therapeutic benefits in myocardial and renal ischemia/reperfusion (I/R). However, the role of SA in intestinal I/R injury is unclear. Thus, the present study aimed to investigate the protective effect of SA against intestinal I/R injury. Caco-2 cells were incubated with different doses of SA before oxygen-glucose deprivation/reoxygenation (OGD/R) induction. The viability of Caco-2 cells, the activity of lactate dehydrogenase (LDH), the production of pro-inflammatory cytokines and the levels of reactive oxygen species, superoxide dismutase and malondialdehyde were measured. Apoptosis was evaluated using a TUNEL assay and western blotting. Transepithelial electrical resistance and western blotting were performed to evaluate intestinal barrier function in Caco-2 cells. The present study revealed that pretreatment with SA significantly increased cell viability and reduced LDH release in Caco-2 cells subjected to OGD/R treatment. In addition, SA suppressed OGD/R-induced inflammatory responses by reducing pro-inflammatory cytokine levels. Furthermore, the levels of oxidative stress and apoptosis were ameliorated by SA. SA also alleviated the intestinal barrier disruption exhibited by Caco-2 cells after OGD/R injury. Overall, the present study revealed that SA may potentially protect Caco-2 cells from OGD/R injury, and that this effect may be attributed to its anti-inflammatory and anti-apoptotic activities, as well as its ability to protect the function of the intestinal barrier.Copyright: © Xiang et al.