Salvia miltiorrhiza (Danshen) is perennial plant and commonly used in traditional Chinese medicine to treat numerous diseases like cardiovascular and cerebrovascular diseases, coronary heart disease, myocardial infarction, stroke and some viral diseases. Nevertheless, no study has been conducted on the antiviral properties of crude extract of Salvia miltiorrhiza against Influenza virus. In an attempt to identify new potential anti-influenza virus agents, 200 natural oriental herbal medicines were screened and we found that Salvia miltiorrhiza has a potential anti-influenza effect. Therefore, in this study, we investigated the protective effect of aqueous extract from Salvia miltiorrhiza against divergent influenza A subtypes using murine model of influenza A infection. Effective dose of aqueous extracts of Salvia miltiorrhiza in BALB/c mice displayed higher survival rate and lower lung viral titers when challenged with lethal doses of influenza A subtypes ({A/Aquatic bird/Korea/ W81/2005(H5N2)}, {A/PR/8/34(H1N1)}, {A/Aquatic bird/Korea/W44/2005(H7N3)} and {A/Chicken/ Korea/116/2004(H9N2)}). In vivo results exhibited that Salvia miltiorrhiza induced prophylactic effect in BALB/c mice against Influenza virus by disrupting viral replication or preventing viral infection by creating an antiviral state in the lungs. Taken together, the use of aqueous extracts of Salvia miltiorrhiza as an orally active antiviral agent, will be potential candidates for prophylactic treatments against Influenza A virus for humans and animals.