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This study sought to monitor the dynamic process of lymph node (LN) metastasis with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and to investigate the impact of disease course on the detection of metastatic LNs by IVIM-DWI. Twenty female New Zealand rabbits with 2.5–3.0 kg body weight were studied. VX2 cells and egg yolk emulsion were randomly inoculated into one thigh to induce metastatic and inflammatory popliteal LNs, respectively. Eight rabbits underwent IVIM-DWI (14 b values, 0–2000 s/mm2) 2 h prior to, and 14, 21, and 28 days after inoculation (D0, D14, D21, D28). The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were measured and compared between the metastatic and the inflammatory groups at each time point. Three rabbits randomly chosen from the remaining twelve rabbits were sacrificed at each time point to perform hematoxylin and eosin staining and histologic evaluation. The patterns of dynamic change of D*, ADC, and D were different between the metastatic and the inflammatory LNs. The metastatic group had a lower D* value at D14 (p =.003), and greater ADC and D values at both D21 (p =.001, p =.001) and D28 (p =.021, p =.001), compared to the inflammatory group. The f value of the metastatic group was greater than that of the inflammatory only at D28 (p =.001). IVIM-DWI can reflect the dynamic process of LN metastasis, and disease course has a significant influence on the ability of IVIM-DWI to detect metastatic nodes. [ABSTRACT FROM AUTHOR]