Objective To explore the antiviral effects of Astragalus polysaccharide (APS) on human infection induced by respiratory syncytial virus (RSV) and its possible mechanism. Methods Male 3-week-old BALB/c mice were randomly divided into 6 groups (10 each): control group, RSV group, APS low-, medium- and high-dose groups, and ribavirin group. Mice in control group were given 50 μl normal saline through nasal drip after mild anesthesia, those in other groups were given 50 μl RSV-long virus solution [containing 6.8×10⁶ plaque forming units (pfu)] by nasal drip for 2 hours to establish the model. In addition, mice in APS low, medium and high groups were given 100, 200 and 300 mg/(kg.d) APS by gavage once a day for 5 days; and in ribavirin group were given 46 mg/(kg.d) ribavirin by gavage once a day for 5 days. Mice in control group and RSV group were given equal volume of normal saline by gavage. The changes of body weight and lung index were measured and calculated before and after infection. The virus replication was detected by plaque reduction test. The T cell subset levels in peripheral blood were detected by flow cytometry.ELISA was performed to detect the levels of inflammatory factors interleukin-1β (IL-1β), IL-18 and IL-33. Colorimetry was used to detect the oxidative and antioxidant indexes of lung tissue including superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA), and Western blotting was performed to detect the protein expression of lung tissue. Results Compared with the control group, the body weight decreased (P<0.05), lung index increased (P<0.05), the expression levels of of IL-1β, IL-18 and IL-33 in serum and the lung tissue oxidation index MDA increased (P<0.05), while the expression of antioxidant index SOD and GSH decreased (P<0.05) in RSV group and APS low-, medium- and high-dose groups. In addition, RSV infection increased the proportion of CD4⁺ cells in peripheral blood, decreased the proportion of CD8⁺ cells and increased the ratio of CD4⁺/CD8⁺ (P<0.05),and increased the expression levels of Toll like receptor 4 (TLR4) protein, and promoted the phosphorylation of mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) (P<0.05) in RSV group, APS low-, medium- and high-dose groups and ribavirin group. While compared with RSV group, APS medium- and high-dose groups and ribavirin group could reverse the above changes (P<0.05). Conclusion APS could inhibit RSV replication, regulate immune response, reduce inflammation and oxidative reaction induced by RSV, and this effect may be related to the inhibition of TLR4/MAPK/NF-κB pathway activation.