Objective To compare clinical characteristics of BALB/c mice infected by H7N9 (A/Shanghai/4664T) and H1N1 PR8 (A/Puerto Rico/8/34) virus for providing clues for H7N9 virus pathogenic mechanism researches. Method Each BALB/c mouse was inoculated by 5×10³ TCID50 H7N9 or H1N1 PR8 virus or PBS after anesthetize. The bodyweight change, lung index, viral load and pulmonary pathology were monitored and analyzed. Result BALB/c mice infected with H1N1 PR8 and H7N9 showed clinical characteristic differences. In terms of bodyweight change, both H1N1 PR8 group and H7N9 group were reduced gradually within 7 days post infection (d.p.i), though the bodyweight of H1N1 PR8 group decreased more rapidly than that of H7N9 group. The lung viral loads of H1N1 PR8 group and H7N9 reached peak at 3 d.p.i, and reduced to very low level at 7 d.p.i. Nevertheless, though the H1N1 PR8 group and H7N9 have no significant difference at 3 d.p.i, H7N9 group showed a significantly higher level of viral loads than that of H1N1 PR8 group at 7 d.p.i (P<0.05). For lung pathological aspects, the major lesions of H1N1 PR8 group were infiltration of inflammatory cells and edema; H7N9 group showed mild inflammatory cell infiltration at 3 d.p.i. Subsequently at 7 d.p.i, the mainly lesions of H1N1 PR8 group were abundant of inflammatory cells infiltration with a massive pulmonary edema; H7N9 group showed a large number of inflammatory cells infiltrating in the lung.Conclusion BALB/c mice infected by H7N9 and H1N1 PR8 showed differences in pathogenic characteristics. H7N9 virus showed less mouse adaptability than the H1N1 PR8 virus. We need to consider the impact of virus titre on follow-up evaluation studies for the efficacy of potential H7N9 therapy drug and vaccine.