Abstract: The Pacific oyster, Crassostrea gigas, is an economically important mariculture species in China, settlement and metamorphosis is an essential process for the larval development of the species. The study of molecular mechanism on larval settlement and metamorphosis is helpful for the oyster growing and seeding. In our studies 128 proteins in different expression were screened and 39 proteins identified during the settlement and metamorphosis with two-dimension gel electrophoresis and mass-spectrometric technique, respectively. The function analysis of the different expressed proteins screened and resulted fibroin related to the formation of cilia and the calcium net proteins related to stabilize the intracellular concentration of calcium ions. These provide the molecular data that reveals the degeneration and disappearance of the veliger tissue and cilia of the oyster larvae and the mechanism of calcium ion to effectively induce the attachment and metamorphosis of the larvae. In the meanwhile, we obtained three key protein enzymes as acetyl coenzyme A dehydrogenase, isocitrate dehydrogenase and 3-phosphate glyceraldehyde dehydrogenase, which respectively regulate the important physiological functions of fatty acid β-oxidation, tricarboxylic acid cycle and glycolysis, and two other enzymes, arginine kinase and ATP synthetase that regulate the energy storage and release in the invertebrate. These observations furtherly clarify the molecular mechanism of energy regulation in oyster larvae during the settlement and metamorphosis.