Acaudina molpadioides is a low-value sea cucumber produced from the southeast coast.It is inexpensive and has hypoglycemic, hypolipidemic, and antioxidant activities.However, its effect on fracture healing has not been reported.In this study, Female C57BL/6 mice underwent right tibia open fracture surgery and were randomly divided into model control group, Apostichopus japonicus group (500 mg/kg BW) and Acaudina molpadioides group (500 mg/kg BW).The tests were performed on the 5th, 10th, and 21st days to explore the effect and mechanism of Acaudina molpadioides on the fracture healing process.Serum dynamic test results showed that on the 10th postoperative day, the serum Col10α concentration in the Acaudina molpadioides group was significantly reduced by 19.31% compared with the model group, and the serum MMP13 by 14.91%.It is suggested that compared with the model group, the chondrocytes in the Acaudina molpadioides group changed from proliferation to hypertrophy and differentiation in advance, which accelerated the healing process.H&E staining results show that compared with the model group, the intervention of Acaudina molpadioides and Apostichopus japonicus can promote the formation of fibrous callus on the 5th postoperative day, postoperative The formation of cartilage callus on day 10 and the formation of lamellar bone and the reconstruction of hard callus on day 21 suggest that the intervention of Acaudina molpadioides can accelerate the process of ossification in cartilage.Further q-PCR results showed that on the 10th day after surgery.The intervention of Acaudina molpadioides can activate Ihh and Smads/Runx2 signals, and down-regulate the transcription levels of key factors Ihh, Patched, Gli1, Gli2 and Smad1, Smad4, Smad5, and the transcription of Col10α is significantly down-regulated, suggesting that Acaudina molpadioides intervention can cross the cartilage faster.The hypertrophic stage of the cells enters the period of mineralization and osteogenesis.At this time, the significant increase in the transcription level of the bone growth factor ALP and Col1α also further proves the role of Acaudina molpadioides in accelerating the fracture healing process.Its effect is similar to that of Apostichopus japonicus.In summary, Acaudina molpadioides can regulate cartilage hypertrophy and accelerate the process of intra-cartilage ossification by mediating Ihh-PThrp and Smads/Runx2 signaling pathways to promote fracture healing, and its effect is equivalent to Apostichopus japonicus.This study provides a theoretical basis for the further development of Acaudina molpadioides and its application in fracture healing.