Objective: To investigate the effect of imperatorin (IMP) on the immune function of bladder cancer bearing mice by regulating the growth arrest specific protein 6 (Gas6)/Axl axis. Method: 12 mice were randomly selected from 60 SPF grade male C57BL/6 mice as the control group (CON group). The remaining mice were evenly divided into Model group, IMP group, Gas6 group, and IMP+Gas6 group, with 12 mice in each group. A concentration of 0.2 mL was injected subcutaneously into their left forelimb at a concentration of 1x107/mL murine bladder cancer cell line T739 cell solution (model group and IMP group were injected with T739 stable transfection cell line of control vector, Gas6 group and IMP+Gas6 group were injected with T739 stable transfection cell line expressing Gas6) for modeling. After successful modeling, the IMP group and IMP+Gas6 group received intraperitoneal injection of 5 mg/kg of IMP. The CON group, Model group, and Gas6 group were injected with an equal amount of physiological saline via intraperitoneal injection, once every 2 days, for 5 consecutive times. Measure the volume and weight of mouse tumors. Measure thymus index and spleen index. Serum interleukin-2 (IL-2), y Interferon (IFN-y), vascular endothelial growth factor (VEGF) levels were detected by enzyme linked immunosorbent assay (ELISA). Hematoxylin eosin (HE) staining was used to examine the pathological changes of tumor tissue. T cell subpopulations was detected by flow cytometry. TUNEL staining was used to detect cell apoptosis. Western blot (Western blot) was used to detect the expression of Gas6/Axl pathway related proteins. Results: The tumor cells in Model group were loosely arranged, with pyknosis and Karyorrhexis in different degrees. IMP can reverse this phenomenon, making the tumor cell arrangement become compact again, the degree of nuclear pyknosis increases, and the Karyorrhexis phenomenon decreases. The model group showed a significant increase in tumor volume, tumor mass, CD8+ cell percentage, Gas6, Axl protein levels, and VEGF levels compared to the CON group (P<0.05), as well as thymus and spleen indices, IL-2, and IFN-酌, the percentage of CD4+ cells, CD4+ /CD8+, and tumor cell apoptosis rate significantly decreased (P<0.05). Compared with the Model group, the IMP group had thymic index, spleen index, IL-2, IFN-酌, the percentage of CD4+ cells, CD4+ /CD8+ cells, and tumor cell apoptosis rate significantly increased (P<0.05), while tumor volume, tumor mass, percentage of CD8+ cells, Gas6, Axl protein levels, and VEGF levels significantly decreased (P<0.05). The results of the Gas6 group showed opposite trends to those of the IMP group. The results of IMP+Gas6 group showed that IMP could reverse the tumor promoting effect of overexpression of Gas6 on bladder cancer bearing mice. IMP may improve the immune function of bladder cancer bearing mice by down-regulation of Gas6/Axl signaling pathway, thus producing anti-tumor effect. [ABSTRACT FROM AUTHOR]