Abstract: Objective To explore the protective effect of Cordycepin (3’-deoxyadenosine), a bioactive compound of Cordyceps Sinensis, on injury of podocytes. Methods C5b-9-induced podocyte injury was used as a model of membranous nephropathy \in vitro. This model was established using mouse podocyte cell line——MPC5. Cordycepin was given as an intervention. Ultra-micro morphological changes were observed by electron microscope. F-actin cytoskeleton and expression of nephrin were observed by fluorescence microscope. The phosphorylation of mitogen-activated protein kinase (MAPK) was measured by Western blot. Results Stimulated by C5b-9 for 3 h, MPC5 showed secondary foot processes, with cytoskeleton structure damaged, nephrin relocated from the cell surface to the cytoplasm, and cell signal pathway-p38, JNK and ERK activated. Cordycepin protected foot processes and cytoskeleton structures of podocytes, suppressed the redistribution of nephrin, and inhibited p38/JNK action. Conclusion Cordycepin can protect podocyte from C5b-9-induced injury partly through inhibiting the activation of p38/JNK signaling pathway.