Background: Immunotherapy is one of the most promising approaches of cancer treatment. Objective: The present study was designed to examine the role of irradiated Ehrlich carcinoma cells (vaccine) and IFNα-2b as an immunomodulator in tumor regression. Ehrlich ascites carcinoma cells and 5 groups of female mice were used. DNA fragmentation and Caspase-3 (Cas-3) activity were identified in Ehrlich carcinoma from different vaccinated mice. Tumor size monitoring, TNF-α and CEA levels were evaluated. Oxidative stress and antioxidant markers, histopathological observations, apoptosis and necrosis in tumor tissues were examined. Results: The results obtained revealed significant inhibition in tumor size in female mice treated with vaccine or IFNα-2b either alone or combined. Cas-3 enzymes activities were significantly elevated in different immunized mice as compared with EC mice along with diminished tumor size. Great alterations in oxidative stress, antioxidant markers and apoptotic observations in tumor tissue were recognized after immunizations of mice bearing EC with vaccine and IFNα-2b either alone or in combined. Conclusion: The immunization action of irradiated Ehrlich carcinoma cells (vaccine) and immunomodulator IFNα-2b in tumor regression could be postulated.