Thevetiaflavone, a natural flavonoid obtained from Wikstroemia indica, could improve cell viability and suppresses the leakage of lactate dehydrogenase from the cytoplasm. Further investigation of the mechanisms demonstrated that it decreases overproduction of ROS and ameliorates ROSmediated mitochondrial dysfunction , including collapse of mitochondrial membrane potential and mitochondrial permeability transition pore opening. It reduces the intracellular Ca 2+ level, which is closely associated with mitochondrial function and interplays with ROS. Furthermore, Thevetiaflavone inhibits apoptosis in PC12 cells through upregulating the expression of Bcl2 and downregulating that of Bax and caspase3 in addition to increasing the activity of caspase3. These results further indicate the protective effects of the vetiaflavone in vivo and its application in the clinic.