Objective To explore the mechanism of ovariectomy on signal transduction of neuroendocrine signals in the rat brain. Methods Twenty-four healthy SPF 2-month-old female Sprague-Dawley rats were randomly divided into ovariectomized group and sham-operated group (n=12). Morphological changes of the brain neurons were examined by pathology using HE staining. The content of epinephrine (E), norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in plasma and different brain regions were detected by high performance liquid chromatography (HPLC). Results Pathological examination showed obvious neuron degeneration in the brain of OVX rats. Compared with the sham-operated group, contents of NE and E in the OVX group were lower, especially in the hippocampus and serum. In the OVX rats, HVA level in the thalamus was higher than that in the sham-operated group, while DA content in the cortex was lower. 5-HT was higher in the hippocampus and cerebellum of OVX group when compared with the sham-operated group, and a lower level was observed in the cortex, thalamus and serum. Moreover, the changes of 5-HIAA was in contrary to that of 5-HT. Conclusions Declined secretion of estrogen after ovariectomy induces abnormal synthesis and secretion of main signal molecules (classic neurotransmitters and amino acids) in the brain tissue. Thus, being a model with abnormal neuroendocrine signaling, the OVX rat provides new ideas and methods for research of signal transduction in peri-menopausal syndrome.