Abstract: OBJECTIVE To optimize the preparation of the toad antibacterial peptide liposomes， to prolong its antibacterial effect and improve its safety and stability. METHODS The toad antibacterial peptide was extracted by water extraction method， and the liposomes were prepared by thin-film dispersion. The Box-Behnken Design-response surface optimization method (BBD-RSM) was applied to analyze and screen the prescription， in which the encapsulation efficiency was used as an index. Design Export 8.0.6 Trial software was used to conduct experimental regression analysis to obtain the optimal prescription. Transdermal absorption experiments were used to verify the absorption of liposome. The antibacterial effect was determinated by dissolution inhibition test. RESULTS The optimal parameters for preparing the toad antibacterial peptide liposomes was that the mass of phospholipid was 40 mg， the ratio of phospholipid and cholesterol was 4∶1， the ratio of lipid phase to drug was 4∶1. And the highest encapsulation efficiency of the toad antibacterial peptide was (79.14±0.5)%. After 12 h， their surface retention rate were appropriate 94.0%， possessing high surface retention， which improved the safety and stability of the antibacterial. The antibacterial results showed that the antibacterial time was effectively prolonged by antibacterial peptide liposomes. CONCLUSION The antibacterial effect is effectively improved and the antibacterial time is effectively prolonged by toad antibacterial peptide liposomes.