Some myxosporeans have been demonstrated to be harmful to worldwide aquaculture. However, the proliferation information has remained unclear in the fish hosts. In this study, we utilized the mix-culturing equality to reveal significant difference in disease assistance between two different clones of gibel carp, in which clone D had been cultured for nearly 40 years, whereas clone A(+) was a newly created clone. According to morphological and genetic analysis of isolated spores, the diseasing pathogen was identified as Myxobolus wulii of the genus Myxobolus in Myxosporea. Subsequently, a polyclonal antibody specific to soluble proteins of the purified spores was generated. Using the antibody, we performed immunofluorescence observation of the liver lump sections sampled from the heavily diseased clone D individuals, and found that the liver lumps were completely composed of numerous honeycomb-like cysts, full of maturing and mature myxosporean spores, and almost all of liver tissues were destroyed. Comparative co-localization detection revealed a significantly inducing expression of apo-14 protein around the infected myxosporean sporoplasms and plasmodia, and the inducing level was much stronger in clone A(+) than in clone D. Furthermore, a primarily screening of 15 different major histocompatibility complex class Iα variants also excavated major variants that respectively belong to clones D and A(+). Therefore, these data provide significant information for differences in myxosporean proliferation and disease resistance in fish clone hosts with different genetic background. Further studies on myxosporean development and the mechanism for disease resistance will be very important for preventing and controlling the parasitic myxosporean disease.