Background and Purpose: In acute ischaemic stroke, the amount (and type) of cellular damage underlying diffusionweighted imaging (DWI) lesion appearances is unclear. We summarized all information from experimental studies of DWI in focal ischaemia models. Methods: We systematically reviewed all published studies of DWI in focal ischaemic stroke models. We extracted key experimental details to determine correlations between histological features and DWI lesion characteristics. Results: Of 141 potentially eligible papers (including more than 2,817 animals, mostly rats), details of key experimental methods were unfortunately often omitted. Consistent findings amongst high-quality studies with blinded analysis included: neuronal damage persists or progresses despite early DWI lesion ‘normalisation’; the apparent diffusion coefficient is not very sensitive to the amount of neuronal damage; the ‘brighter’ the DWI lesion, the greater the neuronal damage; and the DWI lesion may reflect glial more than neuronal changes. Anaesthesia and fixation techniques may inadvertently affect these findings. Conclusions: The relationship between cellular damage and DWI lesion appearance, particularly recovery patterns in reperfusion experiments, remains imprecise. Key experimental details could be reported more completely and consistently. Potential problems from repeated anaesthetics need to be addressed. Early DWI lesion ‘recovery’ in acute stroke patients may largely reflect glial rather than neuronal ‘recovery’. Copyright (C) 2005 S. Karger AG, Basel.