Propofol (PPF) has previously been shown to inhibit the inflammatory response to septic shock. The main purpose of the present study was to investigate the effects of PPF on the levels of regulatory T cells (Treg) and Th17 in septic shock. Septic shock in rats was induced by intraperitoneal injection of lipopolysaccharide (LPS), and PPF (100 mg/kg) was administered. Mortality, the mean arterial pressure (MAP) and heart rates (HR) were recorded for 24 h after LPS injection. The Treg and Th17 ratios were analysed by flow cytometry. Moreover, the expression of p-STAT3, p-STAT5, STAT3, and STAT5 in PBMCs was measured by western blotting. The results showed that the MAP and HR of the PPF group were more stable than those of the LPS group. Mortality at 24 h after LPS injection was much lower in the PPF group compared to that in the LPS group. PPF significantly reduced the levels of IL-17, TNF-α and IL-6 but increased the IL-10 concentration. Moreover, PPF-treated rats exhibited a higher level of circulating Treg cells and a lower level of circulating Th17 cells in comparison to untreated rats. PPF decreased the level of phosphorylated STAT3 (p-STAT3), increased the level of p-STAT5, but did not change the levels of STAT3 and STAT5. Our data suggest that PPF regulates the imbalanced level of Th17/Treg in septic rats, possibly through modulating the expression of p-STAT3 and p-STAT5.