Circulating cell-free DNA (cfDNA) has been widely suggested as clinical indicator in diseases, including sepsis. It was thought that the cfDNA was coming from the cell lysis, necrosis and apoptosis caused by tissue damages during sepsis. M1 or M2 macrophage-type responses kill or repair in vivo, which is highly relevant with the tissue damages in sepsis. The correlation between cfDNA and M1/M2 responses during sepsis was never investigated. Here, we used bacteria injection induced septic peritonitis mouse model in both M1-dominant C57b1/6 and M2-dominant Balb/c mouse strains. We found that M2-dominant Balb/c mice showed better prognosis of septic peritonitis than C57b1/6 mice, which is corresponded with lower level of cfDNA in septic Balb/c mice compared to septic C57b1/6 mice. By assessing the M1 and M2 related cytokines in both septic Balb/c and C57b1/6 mice, we found out that Balb/c mice has lower tumor necrosis factor alpha (TNF alpha) and higher interleukin 10 (IL-10) productions than C57b1/6 mice during septic peritonitis. Especially, when monitoring the monocyte subtypes in peripheral blood of these septic mice, we found out that C57b1/6 showed higher inflammatory (Ly6C(high)) monocyte (corresponding to M1 macrophage) proportion than Balb/c mice. Interestingly, we find out that cfDNA is highly correlated with the ratio of Ly6C(high) monocytes versus Ly6C(low) monocytes, which represents M1/M2 (killing/healing) responses. Our study suggested that the cfDNA is a good indicator for evaluating M1/M2 responses in septic peritonitis. (C) 2016 Elsevier Inc. All rights reserved.