Abstract: Objective: To investigate the protective effects of collagen polypeptides with different molecular weights from Cucumaria frondosa on neural cells damaged by oxidative stress.Methods: Well- differentiated PC12 cells had been cultured in vitro,to establish an oxidative damage model of neural cells by hydrogen peroxide( H2O2).PC12 cells were pretreated with different concentrations of C1 and C2,accordance with the final concentration 0,12.5,25,50,100 μg / m L. The viability of the cells was measured by MTT method. Cells were then divided into the control group,damage group( H2O2) and collagen polypeptides protection groups( collagen polypeptides + H2O2).The reactive oxygen species( ROS),the content of MDA,the outleakage of lactic dehydrogenase( LDH),the activities of antioxidase and Caspase- 3 in PC12 cells were measured by corresponding kits. Results: When the dose was higer than 50 μg / m L,C1 and C2could promote the growth of PC12 injured by H2O2observably( p < 0.01).The level of intracellular ROS of high dose group cells were decreased significantly( p < 0.05).The LDH release,the content of MDA of middle and high dose group cells were decreased significantly( p < 0.01).The activities of SOD,GSH- Px and CAT of middle and high dose group cells were stimulated remarkably( p < 0.05). The activity of apoptosis factor Caspase- 3 was decreased significantly( p < 0.05).Conclusion: Collagen polypeptides from Cucumaria frondosa could play a neuroprotective role in PC12 cells oxidative damaged by H2O2.The more significant effect of the collagen polypeptides with low molecular weight correlated to their amino acids composition in all probability.