Background: In recent years, neoadjuvant chemoradiation and subsequent surgical resection with total mesorectal excision has been shown to increase local control with decreased toxicity. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluated the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation. Materials and Methods: Thirty-six patients with Adenocarcinoma of rectum (up to 15 cm of anal verge) was enrolled in this phase 2 study. Patients were undergone endorectal ultrasound, abdomino-pelvic and chest CT scan for staging. Then received neoadjuvant concurrent chemo radiation (capecitabine 825 mg/m2 bid in combination with celecoxib 100 mg qid and Radiotherapy “50-50.4Gy/25-28fraction”).Surgery was done 6-8 weeks after Chemoradiation. Acute complications were scored by common toxicity criteria 3.0 and tumor response was graded by tumor regression grade. Results: Of 36 patients, total mesorectal excision was done in 30 patients. Tumor regression grade was reported as:8 patients(26.7%) had grade 0 or complete response, 10 patients (33.3%) had grade 1 or moderate response,9 patients(30%) had grade 2 or minimal response and 3 patients (10%) had grade 3 or poor response. Tumor down staging was 43.3% and Node down staging was 30.8%.No patient had skin reaction or cardio-vascular toxicity. Conclusion: Results indicate celecoxib in combination with neoadjuvant chemoradiation is safe and associated with low toxicity. This combination can promote pathologic complete response, tumor regression grade and T and N down staging in rectal adenocarcinoma.