Neurotransmitters are mediators inside the nervous system responsible for transmitting neural-neural or neural-organs signals. Several neural studies have tried to unveil the role of such mediators whose action extended outside the nervous system such as immune, digestive, circulatory and reproductive systems. The present study aimed to investigate the role of the excitatory-glutamate and inhibitory-GABA transmitters in female rats reproduction including their effects on gonadotropins; luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the sex steroids; estrogen (E2) and progesterone (P4) during the estrous cycle as well. Furthermore, the responsive changes on the ovarian tissue were also studied. Synthetic glutamate and GABA were injected intraperitoneally (ip) in those animals throughout four successive estrous cycles. Interestingly, the ip injections of glutamate increased the levels of LH, E2 and P4 but decreased those of FSH significantly. However, the ip injections of GABA significantly decreased the levels of LH in the 4th cycles and FSH throughout treatment period while it increased the levels of E2 and P4. All changes occurred in those reproductive hormones caused by glutamate has been recovered after cessation of glutamate and GABA injection except FSH, including; the 5th, 6th and 7th cycles. Regarding to histopathological examination, ovaries of treated rats showed deleterious changes. The glutamate-treated rats ovaries showed atrophy of the primary follicles with degenerative changes in those secondary and tertiary follicles with obvious degeneration in the granulosa cell layer with vacuolated cytoplasm. On the other hand, those received GABA showed degeneration of the oocytes with congestion of blood vessels supplying the corpora lutea (CL) associated with endothelial changes. The histopathological changes in CL have been improved after glutamate cessation while not changed after GABA cessation.