To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance (MR) imaging in the quantitative assessment of the therapeutic efficacy of a vascular disrupting agent (VDA) (CKD-516) in rabbit VX2 liver tumors. The institutional animal care and use committee approved this study. In 21 VX2 liver tumor-bearing rabbits, IVIM DW imaging examinations were serially performed with a 3.0-T imaging unit by using 12 b values from 0 to 800 sec/mm(2). The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*) of tumors at different time points (baseline, 4 hours, 24 hours, 3 days, and 7 days after CKD-516 administration) were compared within the treated group (n = 15) by using the Friedman test as well as between the control (n = 6) and treated groups by using the Mann-Whitney test. Correlation between the change in tumor size and IVIM DW imaging parameters was analyzed by using the Spearman rank test. In the treated group, D* and f significantly decreased at 4 hours and then recovered to baseline at 24 hours, while D significantly increased at 24 hours (P < .005). All IVIM-derived parameters showed no significant differences between the control and treated groups at 3- and at 7-day follow-up. The greater decrease observed in f and fD* at 4 hours correlated with the smaller increase in tumor size during the 7 days of follow-up (ρ = 0.53 and 0.65, respectively; P < .05 for both). The therapeutic effect induced by a VDA could be effectively evaluated by using IVIM DW imaging, and f and fD* may be early predictive indicators of tumor response.