Objectives: Peritumoral inflammatory response has been considered a good prognostic factor for colorectal cancer. However, patients with distal rectal cancer managed by preoperative chemoradiation therapy may represent a subset of patients where this inflammatory infiltrate is present but inactive due to the immunosuppressive action of the neoadjuvant treatment. For this reason we decided to study the effect of the presence of this pathological finding on disease recurrence and survival. Methods: 180 patients with distal rectal cancer managed by preoperative chemoradiation therapy followed by radical surgery were retrospectively reviewed. Patients with peritumoral inflammatory response were compared to patients without this finding. Results: Overall, 37% patients had peritumoral inflammatory response at pathology. The lack of peritumoral inflammatory response was significantly associated with increased patient’s age (60 vs. 56 years; p=0.04) and the presence of mucinous component (13% vs 3%; p=0.02). 5-year overall survival (91% vs 81%) and disease-free survival (57% vs 48%) were not statistically different between patients with and without peritumoral inflammatory response (p=0.5 and 0.3 respectively). Conclusions: Peritumoral inflammatory response is not a favorable prognostic factor in patients with distal rectal cancer following neoadjuvant chemoradiation therapy. Possibly, the immunosuppressive action of chemoradiation therapy may lead to a loss function of the immunological response. The loss of this immunological action may represent a disadvantage of the neoadjuvant approach for the management of distal rectal cancer.