Little is known about the effect of far-infrared rays (FIR) on serotonin and malondialdehyde levels in depressed patients with insomnia. The purpose of this study is to assess the effect of far-infrared rays on depressed people with insomnia. A randomized design was used to determine this effect. A total of 70 inpatients were recruited with the clinical diagnosis of depression with sleep disturbance. In the experimental group, FIR was applied to three chosen acupuncture points by a patch-like sticker for a period of 15 minutes twice a week. The three acupuncture points are Nei-Kuan (PC6), Shenmen (HT7) and Sanyinjiao (SP6). The total duration of experiment was four weeks. For both experimental and control groups, serum levels of serotonin (5HT) and malondialdehyde (MDA) were examined before and after the introduction of FIR. The experimental group revealed disparate changes over different dependent variables, in which serotonin increased but MDA decreased after the introduction of FIR. These observations indicate that the serotonin pathway is involved in the pathophysiological mechanism responsible for the damaging effects of MDA on depressed patients with insomnia.