Preferential flow, which primarily drains via vertical and interconnected macropores under gravity, allows water and solutes to transport non-uniformly through the soil matrix. Such a feature exacerbates the leaching risk of pollutants to groundwater. However, there is still a lack of knowledge of how the soil macropores affect the migration of manure-sourced veterinary antibiotics (VAs) in agricultural soils. This study used a series of techniques, including field dye tracing experiments, measurements of soil water retention curves (SWRCs), and micro-CT scanning, to explore macropore characteristics for a typical Entisol. The leaching behavior of sulfadiazine (SDZ) and sulfamethazine (SMZ) was then investigated using undisturbed columns (15 cm ID x 20 cm) under simulated rainfall. The results revealed the great lateral diffusion ability of the soil (up to 65 cm) as compared to vertical penetration (50 cm depth) in the field. The soil was abundant in macropores with equivalent diameter > 200 mu m, and the macroporosity was higher in the lower layer (40-60 cm) than the upper layers, where cultivation may lead to the fragmentation of the soil structure and the formation of more isolated pores. Breakthrough curves (BTCs) and hydrological modeling indicated a faster penetration time and greater leaching of sulfonamides with increased macropores in the soil. Such an effect was, however, strengthened under rainstorm conditions (25 mm h(-1)). Antibiotics leaching was strongly correlated with the mean macropore diameter (MD), compactness (CP), and connectivity (Gamma) parameters and significantly affected by MD and CP (p < 0.05), particularly at a moderate rainfall intensity (11 mm h(-1)). This study has linked antibiotics migration with the soil structure and highlighted macropores' contribution to their accelerated leaching, thus providing evidence for environmental risk assessments and promoting sustainable soil and water management in real scenarios of soil macropore flow.