Seasonal influenza is an acute viral infection caused by influenza virus, which is often prevalent in the summer and winter. The influenza virus can infect pigs and poultry. Some literature reports that the influenza virus has an outbreak in summer. The summer climate is characterized by a high humidity and high temperature environment, which is the same as many animal feeding and growing environments. We established a flu animal model under a high temperature and humidity environment during the day to observe the impact of high humidity and high temperature environment on the mice after contracting the influenza virus. Our results indicate that the intestinal flora of 16 s rDNA cultured in High humidity and high temperature environment changes, the intestinal mucosal permeability increases, the expression of pIgR, sIgA, and IgA in the intestinal mucosal immune system decreases, and the NLR immune recognition signaling pathway NOD1 is activated. The expression of related genes such as NOD2, NF-κB, and pIgR increases, which leads to the increase of related inflammatory factors in the vicinity of the intestines, aggravating local inflammation. High humidity and high temperature environment can cause the expression of inflammatory cytokines in the body to rise, causing Th17/Treg immune imbalance, inhibiting Treg maturation and differentiation, and increasing the expression of IL-2, IL-6, and other cytokines, while the expression of IFN-γ and IL-17A decreases. This condition worsens after infection with the influenza virus. Overall, our study found that High humidity and high temperature environment affect the intestinal flora and the body´s immune status, thereby aggravating the status of influenza virus infection.