Infectious skin diseases are a type of inflammatory skin lesions caused by pathogenic microorganisms. Because of the uncertainty of methodology, the skin infection model usually have low replication rate and lack of good evaluation system. We aimed to establish multi-index and comprehensive evaluation method for Staphylococcus aureus (S.aureus) skin-infection models through Analytic hierarchy process (AHP) and Delphi method, and screen high quality animal models through it.Firstly, the evaluation indicators of skin infection were collected basing on literature research. The weight of the evaluation indicators were decided according to AHP and Delphi method. Then different ulcer models (mouse or rat) infected by S. aureus were selected as the research objects.The evaluation indicators were classified into four groups of criteria (including ten sub-indicators) and given different weights, physical sign changes (0.0518), skin lesion appearance (0.2934), morphological observation (0.3184), etiological examination (0.3364). Through the evaluation system, we screened and found that the mouse ulcer model which caused by a round wound and 1.0 × 1010 CFU/mL (0.1 mL) bacterial concentration got the highest comprehensive score, and also found that the model which caused by a 1.5 cm-round wound and 1.0 × 1010 CFU/mL (0.2 mL) maybe the best rat ulcer model.This study has established an evaluation system based on AHP and Delphi method, also provided the best skin ulcer models selected by this system, the models are suitable for disease research and drug development research of skin ulcer.© 2023 Published by Elsevier Ltd.