Objective To investigate the effect of raloxifene combined with olanzapine on negative symptoms in postmenopausal women with schizophrenia， and to further analyze the relationship between serum estradiol levels and negative symptoms during treatment. Methods A total of 80 consecutive postmenopausal women with schizophrenia were randomly divided into the study group and the control group according to the random number table. The study group received 12 weeks of olanzapine and raloxifene（ 60 mg/d） treatment， and the control group received olanzapine and placebo treatment. Serum estradiol levels were measured before treatment and at 12 weeks of treatment. Psychiatric symptoms were assessed using the Positive and Negative Symptoms Scale（ PANSS）. Results There was no significant difference in total score of PANSS， positive symptom score P， negative symptom score N， general psychiatric symptom G and serum estradiol level between the study group and the control group before treatment（ P＞0.05）； after 12 weeks of treatment， total score of PANSS and negative symptom score N in the study group were significantly lower than those in the control group （P＜0.05）， while serum estradiol level was significantly higher than the control group（ P＜0.05）. The difference of serum estradiol level before and after the treatment in the study group was positively related to the difference of the negative symptom scores N（ r=0.434，P＜0.05）. Conclusions Raloxifene can significantly improve the negative symptoms of postmenopausal women with schizophrenia and change the serum estradiol content， and the change of estradiol content in vivo may be related to the improvement of negative symptoms.