Objectives To investigate the effect of quetiapine on the expression of PDLIM5 mRNA in peripheral blood of patients with bipolar depression. Methods Totals of 21 bipolar depression patients（ patient group） and 23 one-level relatives without mental health were recruted. Patients were treated with quetiapine for 8 weeks. Montgomery and Asperger Depression Rating Scale（ MADRS） was evaluated and PDLIM5 mRNA expression level in peripheral blood was also tested before treatment and 2 weeks，4 weeks， 8 weeks after treatment respectively. Results After 2 and 4 weeks of quetiapine treatment， there was no significant difference in MADRS score in patient group before and after treatment（ P ＞ 0.05）. After 8 weeks treatment， MADRS scores in patient group were significantly decreased， and the difference was statistically significant （P ＜ 0.01）. Before treatment， PDLIM5 mRNA levels in peripheral blood of patient group were significantly lower than those in control group（ P＜0.01）. After 2 and 4 weeks treatment， the expression of PDLIM5 mRNA in peripheral blood of patient group showed no significant change compared with that before treatment. The expression of PDLIM5 mRNA in peripheral blood of patient group increased after 8 weeks treatment， and the difference was statistically significant（ P＜0.05）. There was no significant correlation between the total score of MADRS and the expression of PDLIM5 mRNA in peripheral blood of patients with bipolar depression before and after treatment， and the difference was not statistically significant（ P ＞ 0.05）. Conclusions Quetiapine can effectively improve the depressive symptoms of patients with bipolar depression but does not affect the expression of PDLIM5 in peripheral blood.