The present study is undertaken to evaluate the antidepressant activity of Memantine in swiss albino mice. They were divided into four groups containing six mice in each group. First group mice were given normal saline (control) 10ml/kg, Amitriptyline 10mg/kg as standard for second group and for third group Memantine 3mg/kg (test drug) and Memantine plus Amitriptyline (3mg/kg + 10mg/kg) for fourth group intraperitoneally daily for 7 consecutive days. Duration of immobility was observed for 4 minutes in forced swimming test. Duration of locomotor activity was observed in Photoactometer. Results were analyzed by ANOVA followed by Post hoc Tukey’s test. Memantine significantly reduced the immobility time in forced swim test compared to control (p < 0.001). Memantine showed no significant effect on locomotor activity in photoactometer. Memantine showed synergistic antidepressant effect with Amitriptyline. NMDA (N-methyl-D-aspartate) antagonist, Memantinehas showed significant antidepressant activity in experimental models of depression in mice.