Objective: Recent studies have shown that activation of the immune system, inflammatory cell infiltration, and activation of inflammatory mediators play an important role in the development of heart failure. The purpose of this study was to investigate whether cardiac function can be improved by regulating the balance of lymphocyte subsets and cytokines. Methods: Ninety-six patients with chronic heart failure (CHF) who were older than 60 years were randomly divided into two groups: CHF testing group (CHFT) received regular therapy and thymopentin (2 mg thymopentin per day, 15th as a course, three courses in total). CHF control group (CHFC) received regular therapy. Forty-five healthy individuals older than 60 years were used as normal controls. The ejection fraction of left ventricle (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), plasma high sensitive C-reactive protein (hsCRP), plasma brain natriuretic peptide (BNP), 6-min walking distance (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) assessment, lymphocyte subsets, and inflammatory cytokines were tested. Results: The levels of LVEF, 6MWT, CD 3+, CD4+ T cells, natural killer cells, CD4+/CD8+ and IL-10 in CHFT were increased (p<0.01) compared with CHFC, while BNP, hsCRP, MLHFQ, CD8+, TNF-alpha, IL-1 beta, and TNF-alpha/IL-10 ratio in CHFT were decreased (p<0.01). LVEDD and LVESD were decreased, even though there was no significant difference between the two CHF groups. Conclusion: These data suggest that immune modulation therapy improve cardiac function and regulate cytokines and lymphocyte subsets in older patients with CHF.