The aim of our study was to observe the dynamic changes of immunity for patients with severe acute pancreatitis (SAP) and intervention by traditional Chinese medicine. Twenty-three patients who met the inclusion criteria were randomized to combined treatment of traditional Chinese medicine and Western medicine (TCM) or conventional western medicine treatment (WM) groups. The clinical data for all patients were collected. Peripheral venous blood samples were obtained from patients on days 1, 7, 14, and 28 after admission. Biochemical data including the percentage of CD4+/CD8+/natural killer (NK) cells/B lymphocytes/HLA-DR and CD4+/CD8+ ratio in serum were determined by flow cytometer. Patients' characteristics and immunity at admission were similar between the two groups. The secondary infection was different. The levels of T-lymphocyte subsets in the TCM group were quite different from the WM group, with much more the percentage of CD4+ and the CD4+/CD8+ ratio on days 7, 14, and 28 and much less the percentage of CD8+ on days 4 and 28. On days 14 and 28, the levels of NK cells and B lymphocytes were significantly higher in the TCM group compared with the controls. Compared with the TCM group, the levels of HLA-DR were significantly decreased in the WM group on days 7, 14, and 28. The immune dysregulation exists in the development and progression of SAP. The combined treatment of traditional Chinese medicine and western medicine can upregulate the patient's immune and maintain the immune balance.