Abstract: OBJECTIVE To synthesize 6 kinds of fluorine-containing morpholinol derivatives and to explore their antidepressant activity. METHODS The target compounds were synthesized from trifluoromethyl substituted propiophenone via bromination, amination, cyclization, reduction, acidification. The antidepressant activity of all synthesized compounds were evaluated by the forced swimming test in mice. RESULTS The structure of target compounds were identified by ¹H-NMR, IR and MS. The immobility time of compound Vb and Ve were significantly shorter than the blank control group(P<0.05). CONCLUSION This synthetic process is simple and easy to control. Compound Vb and Ve have shown some antidepressant activities.