Objective To investigate the changes of estradiol（ E2） and prolactin（ PRL） levels before and after treatment and their relationship with clinical efficacy in bipolar disorder patients. Methods A total of 57 patients（ 36 male， 21 female） who met the diagnostic criteria of international disease classification （Tenth Edition）（ ICD-10） for bipolar disorder in Beijing Huilongguan Hospital from January 2014 to May 2015 were recruited， among which there were 39 cases of bipolar mania and 18 cases of bipolar depression. After admission， patients were treated with drugs for 6 weeks. Depressive symptoms were assessed by Hamilton Depression Scale-24 items（ HAMD-24）， and manic symptoms were assessed by Bech-Rafaelsen Mania Rating Scale（ BRMS）. The serum E2 and PRL levels in peripheral blood were detected by chemiluminescence immunoassay. Results Compared with the baseline， the PRL level decreased after the treatment， and the difference was statistically significant（ P=0.01）， while there was no significant increase in E2（ P＞0.05）. The PRL of the mania phase group decreased， and the difference was statistically significant（ P=0.01）. The changes in PRL and E2 of the depression phase group were not significant（ P＞0.05）. After the treatment， the BRMS score of mania phase group and HAMD score of depression phase group were statistically decreased， and the differences were statistically significant（ P ＜ 0.01）. A positive correlation was found between PRL levels and scores of BRMS before treatment in mania phase group（ r=0.41，P＜ 0.01）. The change level of PRL and E2 before and after treatment in mania phase group was positively correlated with the reduction of BRMS score （r=0.39，P ＜ 0.01；r=0.33，P=0.03）. Conclusions PRL level decreased after the psychiatric medicine treatment in bipolar disorder patients and mania phase patients. There is a correlation between the level of PRL and the manic symptoms and curative effect.