Graduated compression stockings (GCS) have been employed for several decades to prevent and treat venous diseases of the lower extremities in humans. In order to investigate the mechanism of action of GCS on the lower extremity, a biomechanical model was constructed to simulate the magnitude and distribution of stresses exerted by GCS on the soft tissues, bones, and saphenous veins of the calf. The saphenous vein at the ankle was intercepted, and a flow-solid bidirectional coupling model was established to study the effects of GCS on blood flow return. The results demonstrate that the custom-made GCS can apply pressure to the calf in a manner that is consistent with the desired gradient distribution. The simulated and experimental values of the GCS exerting pressure on the calf surface exhibit a similar variation trend. Furthermore, the application of a GCS has been demonstrated to enhance blood return in the saphenous vein and to elevate the velocity of blood flow. The greater the external pressure applied to the calf, the greater the blood flow velocity of the vein in the calf. The discrepancy between the simulated and experimental values of the blood flow velocity is approximately 8%. The results provide valuable insights into the magnitude and distribution of pressure exerted by the GCS on each part of the calf, confirm the effectiveness of the GCS in promoting blood flow back to the calf veins, and lay the foundation for the accurate design and promotion of GCS.