<p>Elevated intravesical pressure during transurethral resection of bladder tumor (TURBT) is hypothesized to facilitate the release of circulating tumor cells (CTCs), potentially increasing the risk of hematogenous metastasis. However, the causal relationship between intravesical pressure and CTC dissemination remains unclear.&#xa0;This study aimed to investigate the effect of different intravesical pressure levels on the release of CTCs in an orthotopic mouse model of bladder cancer.&#xa0;An orthotopic bladder cancer model was established in female C57BL/6 mice by implanting MB49-luc cells. Tumor-bearing mice were randomly assigned to three groups (<i>n</i> = 6 per group) subjected to different intravesical pressures for 20&#xa0;min: 0 cmH₂O, 40 cmH₂O, and 80 cmH₂O. Peripheral blood was collected 24&#xa0;h post-intervention for CTC detection. CTCs were isolated and identified as CD45⁻/EpCAM⁺ cells using flow cytometry.&#xa0;The release of CTCs into the peripheral blood was significantly promoted by elevated intravesical pressure. Mice in the 40 cmH₂O and 80 cmH₂O groups showed a significantly higher proportion of CTCs compared to the 0 cmH₂O control group. Furthermore, the 80 cmH₂O group demonstrated a significantly greater increase in CTCs than the 40 cmH₂O group, indicating a pressure-dependent effect.&#xa0;Increased intravesical pressure directly promotes the release of CTCs in bladder cancer in a pressure-dependent manner. These findings provide experimental evidence supporting the “pressure-driven CTC dissemination” hypothesis and highlight the potential clinical importance of monitoring and controlling intravesical pressure during surgical procedures to minimize the risk of tumor cell spread.</p>