Purpose: To evaluate the clinical efficacy of imatinib mesylate plus radiotherapy for the treatment of acute leukemia and its effect on immune function.Methods: A retrospective study was conducted on 88 patients with acute leukemia admitted to Zhuji Affiliated Hospital of Shaoxing University between July 2017 and July 2021. They were assigned (randomly, 1:1) to a control group (radiotherapy) or a study group (imatinib mesylate plus radiotherapy) according to different treatment regimens. Outcome measures assessed included the clinical efficacy of the treatments in the patients and their immune functions.Results: The two groups did not show any significant differences with regard to general patient profiles. After treatment, both groups presented reduced white blood cell (WBC) and platelet count (PLT) and elevated red blood cells count (RBC). The level of hemoglobin (Hb) level showed a slight decline in the control group but a significant increase in the study group (p < 0.05). The study group showed better improvement in the levels of WBC, PLT, RBC, and Hb than the control group (p < 0.05). The absolute values of peripheral blood mature neutrophils decreased in both groups after treatment, down to the lowest level at week 2, but rebounded, with higher absolute values in the study group at weeks 2, 3, and 4 of treatment (p < 0.05). Imatinib mesylate plus radiotherapy was associated with higher efficacy, compared with radiotherapy alone (p < 0.05).Conclusion: Radiotherapy plus imatinib mesylate effectively enhances the immune functions of acute leukemia patients, mitigates inflammatory responses, alleviates clinical symptoms, and boosts clinical efficacy. Further clinical trials are, however, required prior to general application in clinical practice.