The diffusion parameters in rat cortex were studied 3–35 days following a cortical stab wound, using diffusion-weighted MR to determine the apparent diffusion coefficient of water (ADCW) in the tissue, and the real-time iontophoretic tetramethylammonium (TMA) method to measure the extracellular space (ECS) diffusion parameters: ECS volume fraction and the ADC of TMA+ (ADCTMA). Severe astrogliosis was found close to the wound, and mild astrogliosis was found in the ipsilateral but not the contralateral cortex. Chondroitin sulfate proteoglycan (CSPG) expression was increased throughout the ipsilateral cortex. In the hemisphere contralateral to the wound, , ADCTMA, and ADCW were not significantly different from control values. ECS volume fraction was increased only in the vicinity of the wound, in the region of cell death and severe astrogliosis, at 3 and 7 days after injury. However, both ADCTMA and ADCW were significantly decreased after lesion in the vicinity of the wound as well as in the rest of the ipsilateral hemisphere distant from the wound. Thus, both ADCW and ADCTMA decreased in regions wherein did not change but CSPG increased. An increase in extracellular matrix expression may therefore impose diffusion barriers for water as well as for TMA molecules.