ObjectiveTo investigate activation of phosphatidylinositol 3 hydroxykinase (PI3K)/AKT pathway and sphingosine 1-phosphate receptor 2 (S1PR2) in peripheral blood mononuclear cells (PBMCs) of acute obstructive cholangitis (AOC) rats and their effects on systemic inflammation in rats.Methods① In vitro experiment: The isolated PBMCs from the rats were divided into 4 groups: a control group, LY294002 treatment group, lipopolysaccharide (LPS) treatment group, and LPS+LY294002 treatment group. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant were detected and the phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the PBMCs were detected. ② In vivo experiment: The rats were randomly divided into four groups: a control group, LY294002 treatment group, AOC model group, and AOC+LY294002 treatment group. The survival rate of rats was recorded, the liver function (ALT, AST, and TBIL), TNF-α, and IL-6 levels in the serum were detected. The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the PBMCs of the rats were detected. Results① The results of in vitro experiment: The levels of TNF-α and IL-6 in the LPS+LY294002 treatment group were significantly lower than those in the LPS treatment group (P<0.050). The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the LPS+LY294002 treatment group were significantly lower than those in the LPS treatment group (P<0.050). ② The results of in vivo experiment: The survival rate of rats in the AOC+LY294002 treatment group was higher than those in the AOC group. The serum levels of ALT, AST, TBIL, TNF-α, and IL-6 in the AOC+LY294002 treatment group were significantly lower than those in the AOC model group (P<0.050). The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the AOC+LY294002 treatment group were significantly lower than those in the AOC model group (P<0.050).ConclusionInhibition of activation of PI3K/AKT pathway in PBMCs can inhibit expression of S1PR2, then alleviate systemic inflammatory response induced by AOC in rats.