The amelioration of secondary neurological damage is among the most important therapeutic goals for patients with intracerebral hemorrhage (ICH). Secondary injury of the ipsilateral substantia nigra (SN) and pyramidal tract (PY) is common after cerebral stroke. Such injury has been characterized previously by anatomical or diffusion MRI, but not in a comprehensive manner, and the knowledge regarding the contralateral changes is relatively poor. This study examined longitudinally both contralateral and ipsilateral SN and PY changes following experimental ICH with diffusion tensor imaging (DTI) and histology. ICH was induced in 14 Sprague-Dawley rats by the infusion of collagenase into the right striatum. Four-shot, spin-echo, echo-planar DTI was performed at 7 T with a b value of 1000 s/mm(2) and 30 diffusion gradient directions at 3.5 h and days 1, 3, 7, 14, 42 and 120 after ICH. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ(//) ) and radial diffusivity (λ(┴) ) were measured in SN and PY accordingly. Two to three rats were sacrificed at days 3, 7, 42 and 120 for histology. The contralateral SN showed an increase in λ(//) with perivascular enlargement during the first 3 days after ICH. The ipsilateral SN showed increases in FA, λ(//) , λ(┴) and MD at day 1, dramatic decreases at day 3 with neuronal degeneration and neuropil vacuolation, and subsequent gradual normalization. The contralateral PY showed diffusivity decreases at day 1. The ipsilateral PY showed early decreases and then late increases in MD and λ(┴,) and continuously decreasing FA and λ(//) with progressive axonal loss and demyelination. In summary, DTI revealed early bilateral changes in SN and PY following ICH. The evolution of the ipsilateral parameters correlated with the histological findings. In the ipsilateral PY, λ(//) and λ(┴) changes indicated evolving and complex pathological processes underlying the monotonic FA decrease. These results support the use of quantitative multiparametric DTI for the evaluation of SN and PY injuries in clinical and preclinical investigations of ICH. Copyright © 2013 John Wiley & Sons, Ltd.