Live influenza vaccine (LAIV) is an effective tool in the fight against influenza infection. LAIV is easy to administer, economical and fast to produce, and stimulates a systemic and local immune response. The aim of the study was to study the early protective effect of LAIV in mice against homologous and heterologous influenza infection within one week of LAIV immunization and possible pathways of immune system activation. We studied expression of early cytokines and type I interferons in response to LAIV introduction in THP-1 cell line. Mice were immunized intranasally with the vaccine virus A/17/South Africa/2013/01(H1N1)pdm09 at a dose of 6 lg EID50. The production of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and type I interferons in the respiratory tract of mice was determined by ELISA. Infection was carried out on the 3rd or 5th day after immunization with the influenza viruses A/South Africa/3626/2013(H1N1)pdm09 or A/Indonesia/5/2005(H5N1) IDCDC-RG2. When both the vaccine virus and the parent virus A/South Africa/3626/2013(H1N1)pdm09 were introduced into THP-1 cell culture, an increase in the expression of type I interferon was observed. Immunization with LAIV lead to increase in the production of early cytokines and type I interferons in the respiratory tract of mice. The mice were completely protected on 5 after immunization against lethal homologous and heterologous influenza infection and partially protected on day 3. The data obtained may indicate the benefit of using LAIV during the seasonal increase in acute respiratory viral infections due to stimulation of innate immune factors.