Objective To investigate the effect and mechanism of oridonin (Ori) on the healing of bone fracture with seawater immersion (BFSI).Methods A total of 72 male C57BL/6 mice (6-8 weeks old) were used to construct BFSI model mice,and then they were randomly divided into bone fracture (BF) group,BF+Ori group,BFSI group,and BFSI+Ori group,with 18 mice in each group.X-ray of femur was taken 14 d after operation and femur mechanical strength test was performed to observe the phenotypic changes of Ori on fracture healing 21 d after operation.The callus tissues of mice were harvested 14 d after operation.The expression levels of the M1 macrophage marker (inducible nitric oxide synthase[iNOS]),M2 macrophage marker CD206,inflammatory factors (cyclooxygenase 2[COX2]and interleukin[IL]-1β),pro-apoptotic factors (cleaved cysteine aspartic acid specific protease[caspase 3]and Bcl-2-associated X protein[Bax]) and anti-apoptotic factor (B-cell lymphoma 2[Bcl-2]) were detected by quantitative polymerase chain reaction (qPCR) and Western blotting.The activation of osteoclasts was observed by tartrate-resistant acid phosphatase (TRAP) staining 7 d after operation.Results The results of X-ray and femur mechanical strength test showed that the fracture healing was significantly weakened in the BFSI group,while Ori significantly improved the healing of BFSI and increased the torsion force of the femur (all P<0.01).The results of qPCR and Western blotting showed that the mRNA and protein expression of iNOS,COX2,IL-1β,cleaved caspase 3 and Bax in the callus tissues of mice was significantly decreased,while the mRNA and protein expression of CD206 and Bcl-2 was significantly increased in the BFSI+Ori group compared with the BFSI group (P<0.05,P<0.01).The results of TRAP staining showed that the number of osteoclasts in the vicinity of the cartilage bone boundary was significantly decreased in the BFSI+Ori group compared with the BFSI group (P<0.01).Conclusion Oridonin can alleviate the inflammatory responses after fracture,reduce cell apoptosis,and inhibit the overactivation of osteoclasts,so as to promote the healing of BFSI by enhancing the polarization of anti-inflammatory M2 macrophages and inhibiting the polarization of pro-inflammatory M1 macrophages.