Objective To investigate the activity and mechanism of Lingzhusan against influenza virus infection in vitro and in vivo.Methods CCK8 assay was used to detect the inhibitory effects of different concentrations of Lingzhusan on influenza virus A/AM/1/47(H1N1),A/Beijing/32/92(H3N2),oseltamivir-resistant influenza virus A strain(H1N1-OC),and respiratory syncytial virus(RSV)in HEP-2 and MDCK cells.In addition,mice were infected with influenza virus A/FM/1/47(H1N1)to investigate the effects of Lingzhusan treatment on survival rate,lung index,lung injury and lung virus titer in mice.By analyzing the contents of IFN-γ,IL-1β and TNF-α in serum and lung tissues,and the activation of NLRP-3/caspase-1 inflammasome pathway,to study the mechanism of Lingzhusan anti infuenza virus infection.Results Lingzhusan showed potent inhibitory effects on four tested virus strains,especially on H1N1-OC and RSV in vitro.Moreover,Lingzhusan could significantly reduce the lung virus titer and inhibit the activation of NLRP-3/caspase-1 inflammasome pathway to alleviate mice death and lung tissue damage caused by virus infection.Conclusion Lingzhusan has a potent inhibitory effect on infection induced by influenza virus.