Objective: To investigate and compare theeffects of different concentrations of morphine, fentanyl and tramadol on the differentiation of human adult helper T cells in vitro. Methods: Twenty out-patients without immune disease were selected and their peripheral blood was collected. Then the whole blood of peripheral blood mononuclear cells (PBMCs) were pretreated with different concentration of morphine, fentanyl and tramadol for 24 h. The level of CD4+ IFN-γ+ IL-2+/CD4+ IL-4+ IL-10+ was analyzed by three-color flow cytometry, and the CD4 + CCR5 + and CD4 + CCR3 + cells were counted to observe the imbalance of Th2/Th2. Results:The number of Th2 increased significantly and the ratio of Th2/Th2 decreased dramatically compared with the control group, and there was a dose-dependent fashion in all drugs. Conclusion: Morphine, fentanyl and tramadol can direct Th0 cells toward Th2 differentiation,especially morphine and fentanyl.