Objective To preliminarily observe the pyroptosis of splenic dendritic cells (DC) in septic mice and its correlation with the levels of inflammatory factors and DC immune function. Methods Seventy BALB/c mice were randomly divided into sham group (n=20), sepsis model group (CLP group, n=30) and caspase (CASP)-1 inhibit group (CLP+YVAD group, n=20). The CLP group and CLP+YVAD group were then divided into CLP 12 h group, CLP 24 h group, CLP 48 h group and CLP 72 h group, and CLP+YVAD 24 h group and CLP+YVAD 72 h group at different time points after operation. Orbital blood was collected from all mice at a predetermined time after operation, and the mice were sacrificed and spleen tissues were extracted. The pyroptosis rate of DC and the expression levels of DC surface markers (CD80, CD86, MHC-Ⅱ) were determined by flow cytometry.Activation of CASP-1 in mouse spleen DC was observed using confocal laser microscope. Western blotting was used to determine the expression of CASP-1 in DC. ELISA was performed to measure the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, and IL-6 in serum. Observe the death of mice after CLP operation. BALB/c mouse T cells were extracted and co-cultured with the mouse spleen DC of each group, the T cell proliferation rate was measured by flow cytometry, and the concentrations of interferon (IFN)-γ, IL-4 and IL-10 in the co-cultured supernatants were detected by ELISA. Results The pyroptosis rate of DC was increased 12 h after CLP compared to sham group (P<0.05), peaked at 24 h (P<0.01), and then progressively declined, but remained higher than sham group at 72 h after CLP (P<0.01). Confocal laser microscopy revealed that the activation of DC CASP-1 in spleen of mice after CLP was obvious. Western blotting showed the expression of CASP-1 in the early stage of sepsis (12 h and 24 h) was significantly higher than that in sham group (P<0.01). After administration of CASP-1 specific inhibitor Ac-YVAD-cmk, the DC pyroptosis rate at CLP+YVAD 24 h group was lower than that in CLP 24 h group (P<0.01). The expression levels of DC surface markers CD80 and MHC-Ⅱ at CLP+YVAD 72 h group were up-regulated compared with CLP 72 h group (P<0.01), and the survival rate of mice at 7 d after operation was improved (P<0.01). The results of ELISA showed that the concentrations of serum TNF-α, IL-12, IL-1β and IL-6 of CLP mice in the early stage (24 h) and late stage (72 h) of sepsis were significantly higher than those in sham group (P<0.01), while the serum concentrations of the above factors in CLP+YVAD group decreased significantly(P<0.01). In the co-culture experiment, compared with DC-CLP 24 h group, the T cell proliferation rate of DC-CLP+YVAD group significantly increased (P<0.01), the level of IFN-γ decrease in co-cultured supernatants, and the levels of IL-4 and IL-10 increased(P<0.01). Conclusions Pyroptosis of DC appears to be activated at the early stage upon septic challenge, might be an important pathophysiological mechanism with regard to the extensive release of inflammatory cytokines as well as immune suppression of DC, which is associated with poor prognosis of sepsis.