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Background The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis. Methods We assessed the survival benefit of daidzein and its effect on lung injury in CLP-induced sepsis in mice and determined the bacterial load in peritoneal fluid, blood, and lung homogenates. Tumor necrosis factor a (TNF-a) and corticosterone levels were measured by enzyme-linked immunosorbent assay; relative mRNA expression was estimated by real-time polymerase chain reaction, and standard biochemical techniques were used to measure nitrite level, myeloperoxidase activity, and vascular permeability. Results Daidzein pretreatment for seven days at a dose of 1 mg/kg body weight subcutaneously increased the survival time of septic mice. Daidzein decreased the bacterial load in peritoneal fluid, blood, and lungs, reduced the tumor necrosis factor a and nitrite level in plasma, and partially suppressed lung injury by reducing vascular permeability and myeloperoxidase activity in septic mice. Further, it restored the relative mRNA expressions of inducible nitric oxide synthase, glucocorticoid receptor a, and glucocorticoid receptor β genes in septic lungs were restored by daidzein pretreatment. Conclusions Daidzein pretreatment for 7 d in sepsis increased the survival time in mice, which may be relate to decrease in bacterial load, anti-inflammatory effect, and protection from lung injury. [ABSTRACT FROM AUTHOR]