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AIM To investigate whether Salvianolic acid A (SAA) exhibits its protective effects in rots through epoxide hydrolase (sEH) and Epexyeicosatrienoic acids (EETs).METHODS Heart and cerebral ischemia in rats were established through the occlusion of left anterior descending coronary artery (LAD) and middle cerebral artery occlusion (MCAO) respectively.SAA 0.3, 1 and 3 mg·kg-1 was administrated before and after operation respectively.RESULTS SAA treatment reduced infarct volume in heart and brain, improved cardiac function, and ameliorated neurological deficits.Notably, the beneficial effects of SAA were attenuated by co-administration of 14,15-EEZE, a putative selective EETs antagonist.Moreover, SAA increased the 14,15-EET levels in the blood,heart and brain of sham and ischemic rats.Assays for hydrolase activity showed that SAA 1 and 3 rag· kg-1 significantly diminished heart and brain sEH activity of ischemic rats.A fluorescent assay in vitro indicated that SAA could inhibit recombinant human sEH activity in a concentration-dependent manner (IC50 =1.62 pmol · L-1).lmmunohistochemical analysis showed that SAA 1 and 3 mg·kg-1 significantly decreased sEH protein expression in heart and hippocampus CA1 region of ischemic rats.CONCLUSION Cardiovascular protection of SAA is mediated at least in part via inhibiting sEH to increase EETs levds.