PURPOSE: We aimed to investigate the changes in intravoxel incoherent motion (IVIM) and diffusion parameters between in vivo and post-mortem conditions and the time dependency of these parameters using two different mouse tumor models with different vessel lumen sizes. METHODS: Six B16 and six MDA-MB-231 xenograft mice were scanned using 7 Tesla MRI under both in vivo/post-mortem conditions. Diffusion weighted imaging with 17 b-values (0-3000 s/mm) were obtained at two diffusion times (9 and 27.6 ms). The shifted apparent diffusion coefficient (sADC) using 2 b-values (200 and 1500 s/mm), non-Gaussian diffusion and IVIM parameters (ADC, K, f) were estimated at each of the diffusion times. The results were evaluated by repeated measures two-way analysis of variance and post hoc Bonferroni test. RESULTS: In B16 tumors, f significantly decreased with post-mortem conditions (from 12.6 ± 6.5% to 5.2 ± 1.9%, P < 0.05 at long diffusion time; from 11.0 ± 2.4% to 4.6 ± 2.7%, P < 0.05 at short diffusion time). In MDA-MB-231 tumors, f also significantly decreased (from 8.8 ± 3.8% to 2.6 ± 1.1%, P < 0.05 at long; from 7.9 ± 5.4% to 2.9 ± 1.1%, P < 0.05 at short). No diffusion time dependency was observed (P = 0.59 in B16 and P = 0.77 in MDA-MB-231). The sADC and ADC values tended to decrease and the K value tended to increase after sacrificing and when increasing the diffusion time. CONCLUSION: The f values dropped after sacrificing, confirming that IVIM MRI is a promising quantitative parameter to evaluate blood microcirculation. The presence of residual post-mortem f values suggested that the influence of water molecule diffusion in the blood lumen may contribute to the IVIM effect. Diffusion MRI parameter's time dependency and those changes after sacrificing could possibly provide additional insights into diffusion hindrance mechanisms.