Introduction: Small intestinal transplantation has been the standard treatment modality for pediatric patient with intestinal failure who failed other surgical and medical treatment. At its current stage, it carries its own risks including but not limited to acute and chronic cellular rejection, graft malfunctions, development of PTLD, viral and bacterial infections. Acute cellular rejection of the intestinal graft is an important and major complication secondary to its rich lymphatic supply. It is usually results from sub therapeutic immunosuppression or non-adherence to medical management. The current management includes modifying the immunosuppression to achieve therapeutic level. Late severe acute intestinal allograft rejection is associated with increased risks of sepsis, bleeding and in the majority of cases with graft loss that ends up in graft enterectomy. We present a case of a 20 year old patient who underwent isolated small bowel transplant for complete intestinal Hirschsprung Disease at age 7 years old, but due to medication non-adherence developed severe late-onset acute cellular rejection manifested by large ostomy OP, fever, weight loss. Underwent ileoscopy on presentation that showed complete loss of normal anatomical intestinal landmarks, bleeding, and ulcerated mucosa. Graft biopsies showed ulceration and granulation tissue with severe architectural distortion, and rare residual consistent with severe intestinal graft rejection. She initially received pulse doses of Intravenous corticosteroids and increased dose of tacrolimus without significant improvement. Her immunosuppression plan was escalated to include infliximab and finally had Antithymocyte globulin (ATG). Graft enterectomy option was entertained frequently during the treatment course; however clinical improvement was noted with evidence of histological improvement and salvage of the graft. The aggressive anti-rejection treatment was complicated with the development of monomorphic, plasmacytoma (PTLD) that was managed with modifying her immunosuppression. Now her graft function is maintained on tacrolimus, oral prednisone, and routine Remicade infusion. Conclusion: 1-Small bowel graft rejection is associated with increased morbidity and mortality, increased risks of sepsis, bleeding and graft loss. 2-We believe that prompt and aggressive immunosuppressive approach significantly increases the chance of rescuing small bowel transplant rejection.