Abstract: OBJECTIVE To observe the effect of Liuwei Dihuang Decoction and three "reinforeing and reducing" herb couples on hypothalamus-pituitary-gonad (HPG) axis and morphologic changes of the gonad in kidney Yin deficiency mice. METHODS The mice were randomly divided into six experimental groups:blank group, model group, Liuwei Dihuang decoction group, Corni Fructus-Moutan Cortex couple group, Rehmanniae Radix Praeparata couple group and Dioscoreae Rhizoma-Poria couple group. The rats were gavaged with oral administration of corresponding medicines for 9 days. On 5-9 d, in addition to the blank group were given distilled water, the other groups were gavaged with hydrocortisone injection per day according to 50 mg·kg^-1 body weight. The contents of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T) were determined by ELISA and radio immunoassay, gonad was observed. RESULTS Compared with blank group, the plasma cAMP, serum FSH, E2, T contents were increased, while plasma cGMP in kidney Yin deficiency were decreased, the difference was statistically significant (P<0.01); gonad tissue damaged. Compared with model group, Liuwei Dihuang decoction and Corni Fructus-Moutan Cortex moutan couple group could increase plasma cGMP, serum FSH, E2, T contents and decrease the plasma cAMP contents(P < 0.05 or P < 0.01), the damaged gonad tissue were repaired. CONCLUSION Liuwei Dihuang decoction could improve kidney Yin deficiency syndrome and regulate the dysfunction of HPG axis, while only Corni Fructus-Moutan Cortex couple is approximate to the whole function; it illustrated that the synergistic action of three "reinforeing and reducing" herb couples are the important basis of Liuwei Dihuang decoction to regulate the HPG axis, which reflects the scientific connotation of the compatibility of the whole herbs.