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Purpose: To investigate the relationship of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) parameters with dysfunction in acute focal cerebral ischemia (ACI) rabbits. Methods: The model of ACI in the middle cerebral artery was made using 30 adult male New Zealand rabbits. The dysfunction severities of the ACI rabbits were assessed using Purdy’s score. A paired-sample rank sum test was adopted to compare the abnormal signal zone (ASZ) volumes from T2 weighted imaging (T2WI), dynamic susceptibility contrast-enhanced (DSC) imaging, and DWI with a relative cerebral blood flow (rCBF) map; correlations were analyzed between the volume of each ASZ and Purdy’s score by Spearman’s rank correlation coefficient. The degree of necrotic and apoptotic cells was evaluated in the ASZ from DWI and DSC PWI-DWI mismatch (PDM) zone. Correlations were analyzed between the index of cellular damage and Purdy’s score, the volume of ASZs by Spearman’s rank correlation coefficient. Results: The ASZ volumes from DSC-PWI and the rCBF maps were larger than those from DWI (p < 0.001 and p < 0.001, respectively); those from the rCBF map (Z = 0.959, p < 0.001) and DSC-PWI (Z = 0.970, p < 0.001) were positively correlated with DWI; a positive correlation was found between Purdy’s score and the ASZ volumes from DSC-PWI (Z = 0.889, p < 0.001), DWI (Z = 0.921, p < 0.001), and rCBF (Z = 0.891, p < 0.001). A significant difference was observed between the ASZ from DWI and the PDM zone in terms of the degree of necrotic (p < 0.001) and apoptotic cells (p < 0.001). The degree of cellular damage in the ASZ of DWI and PDM zone had no relationship with Purdy’s score and the volumes of ASZs. Conclusion: The ASZ volumes from DSC-PWI, rCBF, and particularly DWI reflected the level of dysfunction in rabbits with ACI.