Zinc exhibits antidepressant-like activity in preclinical tests (the forced swim test and tail suspension test) and in olfactory bulbectomy and chronic unpredictable stress; two models of depression. Zinc also enhances the treatment of depression in humans. In the present study we evaluated the antidepressant activity of zinc in another model of depression—chronic mild stress (CMS) and the effect of zinc treatment on BDNF protein and the mRNA level. In CMS zinc hydroaspartate (10 mg/kg) exhibited a rapid (after 1 week of treatment) antidepressant-like effect. Chronic treatment with zinc induced a 17–39% increase in the BDNF mRNA and protein level in the hippocampus. These data indicate a rapidly acting antidepressant-like activity of zinc in CMS and the involvement of zinc in the regulation of BDNF.