〔Abstract〕 Objective To prepare hollow mesoporous silicon nanoparticles(HMSNs) loaded with allicin—diallyl trisulfide(DATS), and to study their feasibility as a therapeutic agent for ischemic injury of lower limbs. Methods HMSNs were synthesized by selective etching, and their microstructure was observed by scanning and transmission electron microscopy. Their physical and chemical properties were analyzed by X-ray diffraction and dynamic light scattering(DLS). Their biological safety was tested by erythrocyte hemolysis and cytotoxicity experiments. DATS was loaded into HMSNs by adsorption to obtain DATS sustained release nanoparticles(DATS-HMSNs), and the cumulative release curve of DATS was calculated and produced by ultraviolet spectrophotometry. C57BL/6 mice were randomly divided into four groups(sham operation group, normal saline group, DATS group, and DATS-HMSNs group). Lower limb ischemia models were made by femoral artery ligation and resection. The exercise ability and the contents of tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), reactive oxygen species(ROS), platelet-endothelial cell adhesion molecule(CD31), alpha smooth muscle actin(α-SMA), basic fibroblast growth factor(bFGF) and vascular endothelial growth factor(VEGF) in muscles of mice in each group before and after limb ischemia were tested. Results Scanning and transmission electron microscope observation showed that the prepared HMSNs were hollow, spherical and uniform in particle size. DLS results showed that the particle size was(226.5±11.8) nm. The results of red blood cell hemolysis test and cytotoxicity test showed that HMSNs had good biocompatibility. The maximum drug loading rate of HMSNs on DATS was 27.89%, the cumulative release rate of DATS in 7 days was about 80.12%, and could reach 97.27% in 21 days. Compared with the control group, after DATS-HMSNs were applied to mice with lower limb ischemia, immunohistochemical staining showed that the levels of CD31, α-SMA, bFGF and VEGF increased(P<0.05). Elisa test showed that the levels of TNF-α, IL-6, MCP-1 and ROS decreased(P<0.05), and the exercise ability of mice recovered satisfactorily after ischemia. Conclusion DATS-HMSNs can release DATS slowly and continuously, providing protection against ischemic injury of lower limbs.