Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.