Aim The relationship between p38 mitogen activated protein(p38-MAPK) and low density lipoprotein receptor(LDLR) in high blood lipid and cerebral ischemia is not clear. This study aims to explore the problem. Methods SD rats were divided into normal diet group and high fat diet group feeding for 30 days and the middle cerebral artery occlusion(MCAO)was induced by the middle cerebral artery occlusion. Serum lipid levels were determined. Neural activity score, infarct weight of ischemic brain tissue and apoptosis, p-p38 expression, LDLR and p-p38 double staining index were determined to observe the effect of high fat diet on the extent of cerebral ischemia. Results Serum TG, TC, LDL of fat diet group were significantly higher than normal diet group. Neural activity score, infarct weight of ischemic brain tissue and apoptosis, p-p38 expression, LDLR and p-p38 expression were significantly higher than normal diet group. Conclusion p-p38 was located in the CA1 region. This experiment from LDLR receptor pathway and p38 MAPK signal pathway (and macrophage inflammatory link ) of two link annotation high blood lipids as risk factors of cerebral ischemiaessence, provides pharmacology reference for the treatment of hyperlipidemia induced by cerebral ischemia.