The settling of particles is related to many industrial processes and research fields. However, due to the complex particle–particle and particle–fluid interactions, the settling mechanism of particles in flowing fluids is not fully understood. This article conducts numerical research on the settling process of two particles with different diameters in parallel in upward flow using the immersion boundary method. The numerical method was validated against experimental results including one particle settling, two parallel particles settling, and two series particles settling. The effects of large particle diameter, upward flow velocity, and initial particle spacing on the settling process were explored. The results indicate that the two particles with same diameter will repel each other when settling in upward flow. Moreover, when the diameters differ, the two particles can experience both attractive and repulsive interactions. The larger the diameter of the large particle, the stronger its attractive influence on the small particle. When the diameter of large particle d2 = 3.0d1, large particle only has an attractive effect on small particle. The wake of each particle forms a distinct velocity boundary with the upward fluid. As the upward flow velocity increases, the interactions between the two particles become increasingly intense. With increasing initial spacing between the particles, their mutual interactions gradually weaken.
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