Objective：This study aims to investigate the effects of progesterone on the expression of NLRP3 and the differentiation of Th17/Treg in murine splenocytes infected by Neisseria gonorrhoeae（Ng）. Methods：Murine splenocytes were isolated in vitro，and randomly divided into five groups：control group，Ng group，Ng+1×10-9 mol/L progesterone group，Ng+1×10-8 mol/L progesterone group，Ng+1×10-7 mol/L progesterone group. The splenocytes were collected after 3 days of culture，the proportions of Th17/Treg cells were detected by intracellular staining using flow cytometry. The mRNA expressions of NLRP3，Th17/Treg-specific transcription factors RORγt and Foxp3 in murine splenocytes were detected by real-time PCR. The protein expression levels of NLRP3，Caspase-1p20，RORγt and Foxp3 in murine splenocytes were determined by Western blot. The concentrations of interleukin（IL）-1β and Th17/Treg related cytokines IL-17，transforming growth facfor（TGF）-β，IL-10 in the supernatant were detected by ELISA. Results：Under the stimulation of Ng，the proportions of Th17 cells and Treg cells，the mRNA and protein levels of NLRP3，Th17/Treg-specific transcription factors RORγt and Foxp3 in the splenocytes，the protein levels of Caspase-1p20 and the concentrations of IL-1β，IL-17，TGF-β and IL-10 in the supernatant increased than those in the controls（P < 0.01）. After pretreated with progesterone，the proportion of Th17 cells，the mRNA and protein levels of NLRP3 and RORγt in the splenocytes，the protein levels of Caspase-1p20 and the concentrations of IL-1β and IL-17 in the supernatant were significantly lower than those in Ng group. The proportion of Treg cells，the mRNA and protein levels of Foxp3 in the splenocytes and the concentrations of TGF-β and IL-10 in the supernatant were significantly higher than those in Ng group（P < 0.01）. Conclusion：Progesterone can inhibit the expression of NLRP3 and Th17 differentiation，and promote the differentiation of Treg cells in murine splenocytes induced by Ng infection.