ABSTRACT: Background/Aims:The ability of regeneration varies widely from invertebrates to vertebrates. Some animals, for example, flatworms, newts, salamanders, and lower vertebrates have the outstanding ability to regenerate all the organs even the whole individual. Unfortunately, the regenerative capacity of humans extremely attenuates along with the biological evolution and this makes it difficult for humans to recover from damaged or missing organs or tissues, and even cause serious loss of function or death. However, the research on regeneration mechanisms is limited and incomplete so far. Here, we investigated the biological mechanisms of zebrafish caudal fin regeneration. Methods:The zebrafish was used as the research object to analyze the differences of mRNA and ncRNA expressed in new tissues at 0d, 3d, and 7d after caudal fin removal, and analyzed the molecular mechanism of caudal fin regeneration from the perspective of the whole transcriptome. Results: We observed that the amputated caudal fin went through a complex genetic change, especially at 3 dpa. This result showed that genes related to response to cell cycle and wounding might play a role in caudal fin regeneration.The up regulated DEGs at 3 dpa (blastema outgrowth stage) were dramatically enriched in 20 Biological Processes (FDR < 0.05), three of which were cell cycle (GO:0007049), mitotic cell cycle (GO:0000278), and cell cycle process (GO:0022402), one was response to wounding (GO:0009611), etc. Conclusion: Taken together, the results revealed that the DEGs were enriched in numerous biological processes, molecular function, cellular component, and signaling pathways, suggesting that the caudal fin regeneration is a highly complicated process of the molecular mechanism.