Abstract:High-mobility group box protein (HMG) is a novel cytokine that takes part in inflammation, cell migration, and tissue damage and regeneration. Regeneration usually involves the regrowth of cells, tissues and organs, and plays an essential role in the survival and adaptation of a species. Sea cucumbers Apostichopus japonicus (Echinodermata, Holothuroidea), which are phylogenetically related to invertebrates, are capable of regenerating damaged organs and body parts, such as the intestine, the respiratory tree, the gonads and the body wall. Sea cucumbers can eviscerate intestines and other organs through the cloaca in response to external stimulations. Within a few weeks after losing an organ or an appendage, the sea cucumber is able to regenerate the missing parts. These animals are thus excellent candidate models for research on organ regeneration. In this study, we analyzed the expression of mRNA and proteins of HMG during the intestine regeneration in sea cucumber using qRT-PCR and immunofluorescence techniques, respectively. The results showed that compared to the control group, there was no significant rise in the expression of either mRNA or proteins of HMG from 30-minute to 6-hour post-evisceration. HMG mRNA expression was significantly upregulated from 1-day to 7-day post-evisceration. The protein expression was higher as well compared to the control group. These results suggested that HMG was involved in the intestine regeneration of A. japonicus and could participate in the activation of the innate immune system in response to tissue damages, and hence was required in the processes such as repair, remolding of extracellular matrix (ECM), and the induction of stem cell migration and differentiation.