In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (GCSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.