Objective To investigate the effect of drug serum of Xijiao Dihuang Combined Prescription (XJDH) on the differentiation of effector T cell (Teff) /regulatory T cell (Treg) in patients with immune thrombocytopenia (ITP), and to investigate the mechanism of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Methods Twenty rats were divided into the drug-containing serum group and the blank serum group by random number table method, with 10 rats in each group. The rats of the two groups were given intragastric administration of XJDH granules and distilled water for 3 consecutive days, respectively. The whole blood samples were collected in the two groups, and drug-containing serum and blank serum were prepared. The peripheral blood samples were collected in healthy volunteers and ITP patients. The peripheral blood mononuclear cells (PBMC) were extracted, and CD4+ T cells were sorted by magnetic beads. After the activation of anti-CD3/CD28 antibody culture system, the cells were divided into the control group, the model group and the experimental group. The control group consisted of CD4+ T cells of healthy volunteers. The model group and the experimental group were CD4+ T cells of ITP patients. The experimental group was treated with drug-containing serum for 72 h, and the control and the model groups were treated with blank serum for 72 h. The proportion of Teff/Treg in CD4+ T cells was detected by flow cytometry in each group. The levels of interleukin (IL-2), interferon (IFN) -γ, tumor necrosis factor (TNF) -α, IL-6, IL-17, Treg cytokine transforming growth factor (TGF)-β and IL10 in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of PI3K, Akt, mTOR and phosphorylated proteins were detected by Western blot assay. Results CD4 positive rate was (99.44±0.01) %. Compared with the control group, the proportion of Teff cells in CD4+ T cells was significantly increased in the model group. The proportion of Treg was significantly decreased, and the ratio of Teff/Treg was increased (P＜0.05). The levels of IL-2, IL-6, IL-17, IFN-γ and TNF-α were increased in the model group, while the levels of TGF-β and IL-10 were decreased (P＜ 0.05), the protein levels of PI3K, p-PI3K, mTOR and p-mTOR were increased in the model group, the level of p-Akt protein was decreased (P＜0.05). Compared with the model group, the proportion of Teff cells in CD4+ T cells was decreased in the experimental group, the proportion of Treg cells was increased, and the Teff/Treg ratio was decreased (P＜0.05). The levels of IL-2, IFN-γ, TNF-α, IL-6 and IL-17 were decreased in the experimental group, while the levels of TGF-β and IL-10 were increased (P＜0.05). Compared with the model group, the protein levels of PI3K, p-PI3K, mTOR and p-mTOR were decreased in the experimental group (P＜0.05). Conclusion The drug serum with XJDH can regulate the differentiation of Teff/Treg and secretion of cytokines in ITP patients, which may be related to the inhibition of expression levels of PI3K, mTOR proteins and their phosphorylated proteins on the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]