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Background: Colorectal cancer is the third common cancer world wide and the forth in Iran. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluate the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation. Methods: Thirty-six patients that have adenocarcinoma of rectum was enrolled (up to 15 cm of anal verge). The patients were undergone Endometrial Ultrasound (EUS), abdomino-pelvic and chest CT for staging. Then received neoadjuvant concurrent chemo radiation (xeloda 825 mg/m2 bid in combination with celecoxib 100 mg qid and 50-50.4Gy/25-28f). Surgery was done 4-8 weeks after chemoradiation. During the chemoradiation the patients was observed for the probable complication one year. Tumor regression grade was reported. Results: From 36 surgery patients, Total Mesorectal Excision (TME) was done in 30 patients. Pathologic complete response was seen in eight of 30 patients (26.7%). Tumor regression grade was calculated in three and five grade system: in three grade system 17 patients had grade 1 (60.7%), eight patients had grade 2 (28.6%) and three patients had grade 3 (10.7%). In five grade system of tumor regression eight patients had grade 1 (28.6%), nine patients had grade 2 (32.1%), eight patients grade 3 (28.6%), three patients had grade 4 (10.7%). T down staging was 43.3%. N downstaging was 30.8%. No patient had skin reaction or cardio-vascular complication. Conclusion: Based on our study results, Celecoxib in combination with neoadjuvant chemoradiation is safe and is associated with low complications. This combination can promote pathologic complete response, TRG and T and N downstaging in Rectal adenocarcinoma. [ABSTRACT FROM AUTHOR]