High potassium diets can improve vascular function yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversal of cerebral artery hypertrophy. Six-week old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK), for 6 weeks; Wistar Kyoto (WKY) rats received the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP (55.1 ± 6.3 vs 71.4 ± 2.4 % of the hemisphere infarcted, HK-SHRSP vs. LK-SHRSP p<0.05). WKY rats had smaller infarcts than both SHRSP groups (33.5 ± 4.8 %). The vessel wall of MCAs from LK-SHRSP were hypertrophied compared to WKY rats; this was reversed in the HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that the expression of the platelet derived growth factor (PDGF) receptor-, PDGF receptor-, epidermal growth factor receptor (EGFR), collagen I and III was increased in the vessels from the LK-SHRSP compared to WKY and were reduced in the HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.