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Diffusion tensor (DT) imaging measures the random molecular diffusion of water in vivo and provides information on the microstructure of tissue. Ischemic brain damage leads to tissue disorganization and structural lost. We aimed to evaluate these changes in a rat model of focal stroke from the hyperacute to chronic phase by utilizing several DT indices. Adult male Wistar rats, subjected to temporary focal cerebral ischemia by suture occlusion of the middle cerebral artery for 90 min, and sham controls were serially imaged at 4.7 Tesla. DT scans were collected repeatedly during the hyperacute (2 and 3.5 h), acute (1, 2, and 3 days), subacute (4, 7, and 14 days), and chronic (4, 6, and 8 weeks) phases. We measured the evolution of DT indices (mean diffusivity (MD), axial diffusivity (λ ║ ), radial diffusivity (λ ┴ ), and fractional anisotropy (FA)) in the cortex, subcortex, and corpus callosum of the ischemic hemisphere. In the hyperacute phase, MD, λ ║ , and λ ┴ reduced with no change in FA. From the acute to subacute phase, MD, λ ║ , and λ ┴ normalized and thereafter increased, whereas FA decreased in all the tissues. In the chronic phase, MD, λ ║ , and λ ┴ continued to rise, whereas FA normalized in the corpus callosum and subcortex, but remained low in the cortex. We described structural tissue changes in ischemic rat brain longitudinally utilizing DT analysis. DT indices reveal different individual patterns reflecting different facades and phases of tissue injury. The use of several DT indices may improve accuracy in estimating the age of the brain injury and in detecting ongoing pathological events.