Tremella Polysaccharides (TPS) have been reported to play an important role in regulating immune responses. Tregs are widely identified as the critical reason for immune dysfunction during sepsis. However, whether TPS could influence the immunomodulatory activities of Tregs in post-burn sepsis mice remains unclear. In this experiment, we researched the effects of TPS on peripheral blood Tregs in sepsis mouse induced by burn plus Pseudomonas aeruginosa infection. Results showed that TPS reversed the influences of Tregs on CD4 + T cells proliferation and polarization and declined the level of IL-10 in burn plus P. aeruginosa infection mice. In addition, TPS notably reduced the mortality of post-burn sepsis mice. Therefore, TPS could inhibit the abnormal activities of CD4 + CD25 high Tregs in burn with P. aeruginosa infection mice, at least in part via inhibiting IL-10 secretion, and trigger a shift of Th2 to Th1 with activation of CD4 + T cells in burn with P. aeruginosa infection mice.