Heavy infection with the ectoparasite Gyrodactylus kobayashii commonly leads to high mortality of ornamental goldfish Carassius auratus. To understand the underlying mechanisms of goldfish against infection of gyrodactylids, transcription responses of immune-related genes including IL-1β2, TNFα1, TNFα2, IFN-γ, TGFβ, MHC II β, TCRβ1 and complement factor C3 were studied by real-time quantitative PCR analysis. Significant increases of expression of inflammatory genes such as IL-1β2, TNFα1, TNFα2 and TGFβ were detected at days 7 and 14 post-infection (pi). No significant differences of G. kobayashii load were observed in response to primary infection and re-infection. In addition, the transcript levels of genes involved in adaptive immunity such as MHC II β and TCRβ1 remained unchanged. Curiously, fish moderately infected with gyrodactylid showed elevated expression IL-1β2, TNFα1 and TNFα2. In all the gyrodactylids-infected fish, expression of complement factor C3 was consistently inhibited. The results extend current knowledge to the understanding of gyrodactylid infection in fish and support the previous findings that innate immunity is indispensable for controlling parasite infection.