This study investigated the changes in cerebral microvessels after ischaemic stroke using a mouse model and light-sheet fluorescence microscopy (LSFM). The transient middle cerebral artery occlusion (tMCAO) mouse model induced local infarcts in the striatum and cortex. The solvent-based clearing method enabled the analysis of the mouse brain microvasculature with LSFM. The mouse brain vasculature was labelled with hydrogel and fluorescein isothiocyanate (FITC)-conjugated albumin via cardiac perfusion. The vascular structure was visualized and quantified with LSFM and a filament-tracing model, which calculated different vascular parameters for healthy and ischaemic tissues. The treatment with the sphingosine-1-phosphate (S1P) receptor modulator FTY720 (Fingolimod) reduced the secondary damage in the infarct area, especially at 14 days post-stroke. FTY720 treatment increased microvascular density and branching point density in the infarct striatum after both mild and severe strokes and decreased infarct volume compared to vehicle treatment, suggesting its potential as stroke therapy.