Objective: To identify the role of interferon (IFN)-γ during respiratory syncytial virus (RSV) re-infection in mice. Method: Female wild type C57BL/6 mice and IFN-γ knockout mice (IFN-γ(-/-) mice) at the age of 6 to 8 weeks were randomly divided into two groups: control group and RSV group, according to random number table.Each group was further divided into primary infection group and re-infection group.There were 8 groups.Mice were sacrificed on days 5, 7, 14 to collect samples.There were 5-8 mice in each group at each time point.And experiment was repeated twice. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, left lung tissues were stained with HE and histopathological scoring (HPS) was performed.The concentrations of IFN-γ, IL-5, IL-13 were determined with ELISA. T test or single factor analysis of variance was used to compare between groups. Result: (1) Mice infected or reinfected with RSV showed pale hair, weight loss, decreased activity and anorexia.(2) IFN-γ levels significantly increased on days 5 and 7 following RSV primary infection and reinfection as compared to control groups in wild type mice ((192±44) vs .(36±8) and (531±161) vs .(23±4) pg/ml on day 5, (100±23) vs .(36±8) and (862±186) vs .(23±4) pg/ml on day 7, t =2.654, 2.513, 2.654, 3.968, all P <0.05). (3) Compared to the RSV-reinfected IFN-γ(-/-) mice, RSV-reinfected wild type mice had less body weight loss ((13.6±2.6)% vs .(22.7±2.9)% on day 5, (18.0±3.1)% vs .(26.5±1.8)% on day 7, t =2.314, 2.308, both P <0.05), lower lung tissue histopathological score ((1.50±0.09) vs .(2.07±0.11) on day 5, (1.53±0.11) vs .(2.08±0.09) on day 7, (1.10±0.06) vs .(1.59±0.08) on day 14, t =3.916, 3.890, 4.837, all P <0.01), less BALF inflammatory cells count ((11.6±2.0) vs .(44.2±10.6)×10(5)/ml on day 5, (18.2±3.9) vs .(38.3±2.2)×10(5)/ml on day 7, t =2.818, 4.786, both P <0.05), and lower levels of IL-5 and IL-13 ((24±3) vs .(148±23), (23±4) vs .(169±26) pg/ml on day 5, (30±8) vs .(233±44), (20±5) vs .(182±19) pg/ml on day 7, (91±6) vs .(129±19), (62±8) vs .(132±5) pg/ml on day 14, t =5.252, 5.445, 4.517, 7.326, 3.816, 7.577, all P <0.01). Conclusion: IFN-γ can alleviate airway inflammation following RSV reinfection in mice.