Abstract: AimTo study the effects of hydroxysafflor yellow A (HSYA) on the mitochondrial function of cortex mitochondrial during cerebral ischemia in rats. MethodsRat focal cerebral ischemia model in rats was established by ligation of middle cerebral central artery. Cortex mitochondria were isolated and prepared for the measurement of membrane fluidity, swelling, respiratory function, activities of mitochondrial respiratory enzymes and superoxide dismutase (SOD), contents of phospholipid，malondial dehyde (MDA) and Ca²⁺ to evaluate the function of mitochondria. ResultsFocal cerebral ischemia resulted in severe neuronal mitochondrial injuries, which could be alleviated by iv HSYA (10, 20 mg·kg^-1), and nimodipine (Nim, 1.0 mg·kg^-1). The swelling of mitochondria was ameliorated, the decomposability of membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased, HSYA also significantly inhibited the decrease in the activities of respiratory enzymes and SOD of mitochondria, and the increase in MDA and Ca²⁺ levels caused by cerebral ischemia in rats. ConclusionHSYA showed a protective action against the cortex mitochondrial injuries in rats induced by cerebral ischemia. The mechanisms may be derived from reducing lipid peroxides, inhibiting Ca²⁺ overload， scavenging free radicals and improving the energy metabolism.