_1788849831 20260908064351000 Rovedar Daryoushbabazadeh@gmail.com Rovedar Journal of Lab Animal Research J Lab Anim. Res 2980-9703 08 30 2026 5 4 Seyed Mohsen Mousavi Fard https://orcid.org/0009-0008-8360-4702 Ali Sarani https://orcid.org/0000-0002-0550-9186 Mohammad Manian https://orcid.org/0009-0003-4353-2242 Ali Hassanzadeh Teroujeni https://orcid.org/0000-0002-0734-3888 Emerging zoonotic diseases have become an increasing concern for global health due to the rising incidence of pathogen transmission from animals to humans. The present study aimed to comprehensively synthesize the current knowledge on zoonotic disease outbreaks and transmission, with a specific focus on evaluating the role, applications, advantages, and limitations of laboratory animal models in this field. A peer-reviewed literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2000 and 2026, supplemented by earlier pivotal studies. The current study evaluated a range of models, including conventional, humanized, and transgenic mice, hamsters, ferrets, guinea pigs, rabbits, non-human primates, and emerging alternatives, focusing on their utility, strengths, and drawbacks for studying host-pathogen interactions, immune responses, tissue tropism, and disease progression. The present study underscored the importance of animal models in the preclinical assessment of antiviral agents, vaccines, monoclonal antibodies, and innovative therapeutic strategies. Recent outbreaks caused by pathogens such as SARS-CoV-2, Nipah virus, H5N1 influenza virus, Mpox virus, Ebola virus, Marburg virus, hantavirus, and Crimean-Congo hemorrhagic fever virus have highlighted the urgent necessity to enhance comprehension of zoonotic disease emergence and transmission. 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