Background: Tailoring therapy is the target in the management of any cancer; if factors which can predict response to treatment are identified, we can individualize treatment. Locally advanced rectal cancer studies reported that tumor microenvironment and host immune response played roles in sensitivity to chemoradiotherapy (CRT) by proving that both peripheral circulating lymphocytes and tumor infiltrating lymphocytes (TILs) strongly correlated with the response rate to CRT and it impacted disease outcome. Aim of the work: We aimed to assess the predictive value of peripheral blood lymphocytes and tumor infiltrating lymphocytes by correlation with regression rate post chemo- radiotherapy in patients with rectal cancer, and to find correlation between peripheral and tissue lymphocytes. Method: Before neoadjuvant, CRT venous blood samples were obtained from 40 patients with rectal cancer, and prior to surgery. Blood cell counts in the samples were analyzed using an automated hematology analyzer and flowcytometry used to analyze lymphocyte subsets. Colonscopic biopsies were obtained before the CRT; the numbers and distributions of T cells (CD4 & CD8) were evaluated by immunostaining. Results: Pre CRT peripheral total lymphocytes, T lymphocytes, T helper, T cytotoxic lymphocytes significantly correlated with tumor regression rate (p = 0.04, 0.05, 0.06, 0.04 respectively). The density of tissue CD4(+) and CD8(+) T cells was highly correlated with tumor regression post CRT (p = 0.01 for both). The high expressions of tissue CD4 & CD 8 were significantly correlated with high number of pretreatment peripheral total lymphocytes, T lymphocytes, Thelper, and T cytotoxic lymphocytes with significant p value for all. Conclusion: We concluded that peripheral lymphocytic count and its subsets have significant correlation to tissue CD4, CD8 and both can predict pathological response to CRT; enhancement of lymphocytes mediated immune response can help for outcome improvement.