[Objective] To study the role of NODs signaling pathway against the stimulate of Aspergillus fumigatus in RAW264.7 cells by using siRNA to silence NOD2 gene. [Methods] RAW 264.7 cells were inoculated in six-well plate, and then divided into four groups: normal control group (N), normal control group with NOD2 gene silence group, normal with Aspergillus fumigatus spores stimulation group (N+Af) and normal with Aspergillus fumigatus spores stimulation with NOD2 gene silence group. Each groups has three duplicate wells. The expressions of NOD1、NOD2 and RIP2 mRNA in each group were studied by RT-PCR and the expression of TNF-α in each group was detected by western blot assay. [Results] Compared with the N group, expressions of NOD1、NOD2 mRNA and TNF-α protein increased significantly in N+Af group; Compared with negative control group, the expression of NOD2 mRNA was sig-nificantly suppressed in NOD2(RNAi) group, the silencing effect was reached to 80%, indicating that NOD2 gene in RAW264.7 cells was succsessfully silenced. Compared with NOD2(RNAi) group, the expressions of NOD1、NOD2 mRNA and TNF-α protein were slightly increased, but no siginifcant difference (P>0.05). Compared with N group, the ex-pression of TNF-α protein was increased significantly in NOD2(RNAi) group; Compared with N+Af group, the expression of TNF-α protein was lowered significantly in NOD2(RNAi)+ Af group. The expressions of NOD1、RIP2 mRNA in each group were changed slightly. [Conclusion] NODs and its signaling pathway play a role in resistance to Aspergillus fumiga-tus in RAW264.7 cells, particularly the role of NOD2 more prominent.