Objective To investigate the effects of different drugs and to explore the mechanism of pain in mice with adenomyosis (ADM). Methods The mouse model of adenomyosis was induced by oral administration of tamoxifen. The vaginal smear was examined by cytology, and serum levels of 5-HT, GnRH-R, NGF and NF were determined. Results Higher level of 5-HT was detected in the controls compared with the models. The expression of GnRH-R and NGF in normal endometrium and eutopic endometrium were significantly lower than those in ectopic endometrium. The expression on NF in normal endometrium was significantly lower than that in the eutopic and ectopic endometria. Conclusions Similar with regular dose of GnRH-a, half dose of GnRH-a can slow down the progress of ADM as well as reducing pain. Combination of regular dose of GnRH-a and Diane-35 could consolidate the therapeutic effect and even achieve pathological cure. 5-HT may take an active part in the mechanism of pain in ADM.