<p>Intestinal ischemia reperfusion (II/R) is an abdominal critical case especially in neonates and during childhood affecting not only the intestinal tissue but also it could damage other remote organs including cardiac tissue even following surgical intervention. Immune homeostasis during II/R has a major role in controlling its progression. Thus, finding additive medical treatment besides the surgical one becomes an urgent need to keep the tissue. So that, we aimed to evaluate the possible ameliorative effect of diacerein (DIA) on II/R-induced injury in juvenile rats. Forty juvenile rats of Wistar albino species were randomly allocated into four different groups: sham group, DIA given group, II/R group via clamping superior mesenteric artery, DIA-treated group (50&#xa0;mg/kg) with induction of II/R. Data of current model revealed a significant elevation of the measured cardiac enzymes, cleaved caspase-3, and nuclear factor kappa β (NF-κB) in the untreated ischemic group with disturbed oxidative stress parameters, accompanied with dysregulation of inflammasome/caspase-1/IL-1β and Wnt/β-catenin signaling cascades. Fortunately, upon co-administration of DIA, there is a significant decrease of cardiac enzymes, cleaved caspase-3, and NF-κB with normalization of oxidative stress parameters and regulation of inflammasome/caspase-1/IL-1β and Wnt/β-catenin pathways confirmed by marked mitigation of the histopathological changes. This effect of DIA is greatly attributed to its pharmacological properties including IL-1β antagonist effect, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Thus, DIA could be considered as an adjuvant future medical therapy for those cases of II/R.</p> Graphical abstract <p></p>