OBJECTIVE We aim to determine the effect of local and systemic administration of kisspeptin-54 on ovarian hyperstimulation. METHODS Immature female rats were used. In order to generate the ovarian hyperstimulation model, 50 IU PMSG was administered for 4 consecutive days and a single dose of 25 IU hCG was administered to all groups except for the sham group. To synchronize the sham group, a single dose of 10 IU PMSG followed by 10 IU hCG (48 h later) was applied. Kisspeptin-54 and gonadotropin-releasing hormone (GnRH) agonists were administered 48 h after hCG injection. While intracerebroventricular injection is performed with stereotaxic surgery, Intravenous administration was from the tail vein. Ovarian weights were measured. FSH, LH, estrogen and progesterone hormones were detected in serum by ELISA. VEGFa, IL-1β, TNF-α, MCP-1 immunohistochemical staining was performed on the ovaries and hypothalamus and their optical densities were determined with Image J. Kiss1R mRNA expression was determined by qRT-PCR. RESULTS Ovarian weights increased significantly in the OHSS group and the systemic GnRH agonist group. The optical densities of VEGFa, IL-1β, TNF- α and MCP-1 immunoreactivity showed us that both local and systemic applied kisspeptin-54 attenuates the level of investigated inflammation parameters in the ovaries. Moreover, local administration of kisspeptin-54 has been shown to enhance the level of Kiss1R mRNA in both the ovaries and the hypothalamus. CONCLUSIONS Local and systemic administration of Kisspeptin-54 as a post-treatment reduces inflammation parameters in the ovaries. These findings promote the potential use of kisspeptin-54 on OHSS.