Cytokines play important roles in heart failure (HF). We examined whether cytokine levels are different in acute decompensated heart failure (ADHF) patients between with left ventricular systolic dysfunction (LVSDF) and with preserved LV ejection function (PLVEF). We studied 81 HF patients who were admitted to our hospital with acute decompensation. They were divided into two groups: LVSDF (LVEF)<45% and PLVEF (LVEF45%). Serum interleukin-6 (IL-6), highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and IL-18 and plasma brain natriuretic peptide (BNP) were measured on admission and at discharge. On admission, IL-6 and hsCRP were higher in LVSDF than in PLVEF. IL-6 and hsCRP decreased after treatment in LVSDF, but not in PLVEF, while plasma BNP levels decreased in both HF with treatment. There was no difference in TNF-alpha or in IL-18 level between LVSDF and PLVEF, and they did not change after treatment in either group. In conclusion, cytokine profiles were different in ADHF between those with LVSDF and PLVEF. Activation of IL-6-hsCRP pathway may play a specific role in ADHF with LVSDF.