We investigated to evaluate whether diffusional kurtosis imaging (DKI) can early detect the microstructure change of corticospinal tract (CST) after unilateral cerebral infarction solely in middle cerebral artery (MCA) territory. Seventy-seven patients with MCA territory infarct consisting of 10 subjects of hyperacute phase, 22 subjects of acute phase, 28 subjects of subacute phase and 17 subjects of chronic phase were enrolled in this study. ROI method was performed to measure the mean value of the infarcted area and the areas which belongs to CST [including the posterior limb of internal capsule (PLIC), cerebral peduncle (CP), pons, and medulla] in both ipsilateral and contralateral mirror side in all the DKI-derived parametric maps. Compared with the contralateral mirror side, MK, K-parallel to, K-perpendicular to in the infarcted area sharply increased to a peak in acute phase, and then gradually fell down. MD, D-parallel to and D-perpendicular to decreased till acute phase and then started to increase gradually. FA decreased more and more seriously from hyperacute to chronic phase. K-parallel to and D-parallel to were more helpful to detect the subtle changes of CST after infarction as they both had significant changes in all phases. Moreover, there were more locations that had significant changes with time going on. To conclude, DKI, especially the variable K-parallel to and D-parallel to, may serve as a new biomarker to observe the microstructure change of the descending CST, which may reflect the extent of Wallerian degeneration and be helpful for clinical decision making.