['We previously reported the promising effects of dioscin against cerebral and renal ischemia-reperfusion (I/R) injury. However, its role against gastric I/R injury has not yet been reported. Thus, the aim of the present work was to investigate the protective effect and possible mechanisms of dioscin against gastric I/R.', 'The hypoxia-reoxygenation (H/R) model in GES-1\xa0cells and the celiac artery occlusion model in rats were carried out in the study.', 'Dioscin markedly attenuated H/R insult in GES-1\xa0cells and gastric I/R injury in rats. Mechanistic studies demonstrated that dioscin-induced gastric protection was accompanied by inhibiting the levels of PKCα, PKCβ2 and phosphorylation via decreasing Raf-1 level. Blockade of PKC/ERK1/2 signaling pathway by dioscin decreased MEK1/2 level, ERK1/2 phosphorylation and the nuclear translocation, NF-κB and AP-1 transcriptional activities, pro-inflammatory cytokine responses, and up-regulated PPAR-γ level. Moreover, the results of small interfering RNA (siRNA) and overexpression of PKCα and PKCβ2 confirmed that dioscin attenuated gastric I/R injury through inhibiting PKC/ERK1/2 signaling by down-regulating PKCα and PKCβ2.'] Does dioscin attenuate gastric ischemia/reperfusion injury through the down-regulation of PKC/ERK1/2 signaling via PKCα and PKCβ2 inhibition?