To investigate the pathogenicity and cross-species transmission potential of H13 and H16-subtype of low pathogenic avian influenza viruses (LPAIVs), two strains of H13N8 and H16N3 isolated from shorebirds were used to infect mice. Clinical signs were observed, and viral loads and cytokine expression levels were measured. The results showed that both H13N8 and H16N3 AIV exhibited low pathogenicity in mice and could replicate efficiently in the rectum of mice without prior adaptation. Compared with the PBS group, six cytokines were expressed at low levels, further confirming the low pathogenicity of the H13N8 and H16N3 strains in mice. The results indicate that both strains have the potential for cross-species transmission to mammals.