Annual fishes of the genus Nothobranchius show expression of age-related biomarkers at behavioral and histological levels. They therefore represent an excellent animal model for aging studies. However, oocyte development, histological and biochemical degeneration and immune response of ovary in the annual fishes remain unclear. Here, using one of these short-lived fishes, Nothobranchius guentheri, we reported that oogenesis process was divided into four stages (oogonium, primary growth stage, cortical alveolus stage and vitellogenesis stage), and old ovaries showed histological degeneration (with decreased mature oocytes and increased atretic oocytes) accompaning with high levels of senescence-associated beta-galactosidase and lipofuscin by down-regulation of vitellogenin (the precursor of yolk proteins). Moreover, poly(I:C) induced inflammation with overexpression of NF-κB and IL-8, and up-regulated vitellogenin expression. It was a first analysis for vitellogenin to participate in ovarian degeneration and immune response in ovary of fish, indicating that vitellogenin fulfilled a critical role in ovary development and innate immune system.