Objective To study effects of flow shear stress combined with salvianolic acid B (Sla B) on anti-platelet aggregation and its possible mechanism under the theoretical framework of biomechanopharmacology. Methods 2×4 factor experimental design was employed. By using Bioflux 1000 microfluidic system, shear stresses of 0.02 Pa and 1.5 Pa were applied together with four levels of Sla B concentration treatment on human vascular endothelial cells (HUVECs) for 20 hours. Then the cell supernatant was collected to detect concentration of 6-keto-PGF1α and vWF by ELISA and their effects on ADP-induced platelet aggregation were tested. Immunofluorescence method was used to detect vWF in endothelial cell cytoplasm. Results Physical shear stress of 1.5 Pa combined with Sla B of 100 μg/mL could significantly promote the endothelial secretion of 6-keto-PGF1α as compared to low shear stress condition (P<0.05). The endothelial cell supernatant under shear stress of 1.5 Pa showed an obvious anti-platelet aggregation effect. As the single factor, shear stresses significantly influenced vWF secretion (P<0.01), but Sla B had no obvious effects on vWF secretion. Conclusions Sla B inhibited ADP-induced platelet aggregation by increasing endothelial secretion of PGI2 under physical shear stresses. From the view of biomechaopharmacology (interaction between blood flow, blood vessel and blood), the physical flow shear stress is beneficial for the anti-thrombosis effect of Sla B.