OBJECTIVE： To investigate the effects of hyperbaric oxygen combined with flupentixol and melitracen on depression improvement， extremity motor function and ability of daily living and activity in patients with post-stroke depression （PSD）. METHODS： 60 PSD patients were divided into control group and observation group according to random number table， with 30 cases in each group. Both groups received routine clinical treatment， comprehensive rehabilitation therapy and psychotherapy. The control group was additionally given Flupentixol and melitracen tablets， orally， one tablet each time， in the morning； 3 days later， one tablet each time， in the morning and noon， for 4 weeks. Other anti-depressive agents were not given during treatment. Observation group was additionally given hyperbaric oxygen， 0.12 MPa， for 90 min， qd， 5 times a week， for 4 weeks， on the basis of control group.  Depression degree [Hamilton depression scale （HAMD） and Self-rating depression scale（SDS）]， extremity motor function [Fugl-Mayer motor function assessment （FMA）] and ability of daily living and activity [modified Barthel index （MBI）] were scored in 2 groups before and after treatment， and ADR was observed. RESULTS： After 4 weeks of treatment， HAMD and SDS of 2 groups were decreased significantly compared to before treatment， while FMA and MBI were increased significantly； the improvement of observation group was significantly better than that of control group， with statistical significance （P＜0.05）. No obvious ADR was found in 2 groups. CONCLUSIONS： Hyperbaric oxygen combined with flupentixol and melitracen can effectively improve PSD， relieve negative emotion and improve extremity motor function and ability of daily living and activity.