A rat model was used to distinguish between the different factors that contribute to muscle tissue damage related to deep pressure ulcers that develop after compressive loading. In the present study the separate and combined effects of ischemia and deformation were studied. Loading was applied to the hind limb of rats for two hours. Muscle tissue was examined using magnetic resonance imaging (MRI) and histology. An MR-compatible loading device was used, which provided the possibility of simultaneous loading and measurement of tissue status. Two separate loading protocols were applied incorporating uniaxial loading, resulting in compression of the tissue, and ischemic loading. Uniaxial loading was applied to the tibialis anterior (TA) by means of an indenter, and ischemic loading using an inflatable tourniquet. Deformation of the muscle tissue during uniaxial loading was measured using MR tagging. Compression of the tissues for two hours led to increased T2-values, which were correlated to necrotic regions in the TA. Perfusion measurements, using contrast-enhanced MRI, indicated a large ischemic region during indentation. Pure ischemic loading for 2 hours led to reversible tissue changes. From the MR tagging experiments local strain fields were calculated. A deformation of 4.5mm, corresponding to a surface pressure of 150 kPa, resulted in maximum shear strain values up to 1.0. There was a good correlation between the location of damage and the location of high shear strain values. It was concluded that the large deformations, in conjunction with ischemia, provided the main trigger for irreversible muscle damage.