Background: Intestinal ischemia/reperfusion (I/R) is one of the factors entailed in multiple organ dysfunction syndrome (MODS) etiology, possibly via disrupting the redox status and/or triggering the inflammatory cascade in intestine, liver and kidney. The management of MODS is becoming more complicated with new medications and new treatment paradigms. Objective: The current study elucidated the possible protective mechanisms of rosuvastatin, known for its pleiotropic effects against intestinal I/R insult. Material and Methods: Animals in the current study were randomly assigned into three groups: the first group served as the sham group, the second was the positive control one (I/R) receiving saline, while the third presented the rosuvstatin- pretreated group. Oral rosuvastatin (10 mg/kg) was given for 3 days before I/R, which was carried out by clamping the superior mesenteric artery for 30 minutes followed by declamping for 60 minutes. At the end of the reperfusion period, blood samples were collected and the tissue homogenate from intestine, liver and kidney were used to determine the effect of rosuvastatin against intestinal I/R insult. Results: In the three organs studied, intestinal I/R elevated lipid peroxide formation and the activities of myeloperoxidase (MPO), proinflammatory cytokines (IL-1B, IL-6) and caspase-3. Also, the insult decreased the activities of both superoxide dismutase (SOD), and glutathione S transferase (GST). Intestinal I/R increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), and creatine kinase (CK). Conclusion: Rosuvastatin pretreatment protected against intestinal I/R-induced alteration in the previous assessed parameters. Apart from its lipid lowering capacity, our data suggested a therapeutic potential for rosuvastatin in attenuating redox status disturbance, triggered inflammation and modulating immune response as well as anti-apoptotic capacity. Also, the study proved the presence of a direct correlation between the extent of target organ damage with the activation of inflammation and induction of apoptosis in gut I/R model. This documented the interplay of several factors in the MODS model, which pointed to the use of certain agents that can control multiple pathways in this disorder.