Spectral domain optical coherence tomography (SDOCT) images have been used to investigate the mechanism of optical clearing in flowing blood using dextrans. The depth reflectivity profiles from SDOCT indicate that dextrans become increasingly more effective in reducing scattering in flowing blood, except for 5 mgdl(-1) of Dx500, with increasing molecular weights (MW 70,000 and 500,000) and concentrations (0.6, 2, and 5 mgdl(-1)). Among the tested dextrans, Dx500 at 2 mgdl(-1) had the most significant effect on light scattering reduction with the strongest capability to induce erythrocyte aggregation. Dx500 at 5 mgdl(-1) contributes more refractive index matching but induces a decrease in aggregation that leads to the same level as 0.6 mgdl(-1) Dx500. Previous studies identified various mechanisms of light scattering reduction in stationary blood induced by optical clearing agents. Our results suggest that erythrocyte aggregation is a more important mechanism for optical clearing in flowing blood using dextrans, providing a rational design basis for effective flowing blood optical clearing, which is essential for improving OCT imaging capability through flowing blood.