In this study, using a rat model of HS, we tried to investigate whether HMGB1-induced activation of NLRP3 inflammasome occurs via its receptors including toll-like receptor 4 (TLR4) and the receptor for advanced glycation end product (RAGE) signaling pathway, and contributes to platelet activation and thrombocytopenia. This evidence concerns the gene HMGB1 and histiocytic sarcoma.