AIMS: To evaluate the antidepressant activity of tapentadol in Swiss albino mice. MATERIALS AND METHODS: Thirty inbred male albino mice weighing 20–25 grams were selected from central animal house. They were divided into five groups of six animals each. The control group I received normal saline 10 ml/kg intraperitoneally, standard group II received fluoxetine (20 mg / kg, intraperitoneally) and test groups III, IV, V received tapentadol in graded doses 10mg/kg, 20g/kg and 40 mg /kg intraperitoneally. Antidepressant activity was assessed by using Forced swim test. The results were tabulated and analysed with suitable statistical method. RESULT: Tapentadol showed statistically significant antidepressant activity at all the three test doses (P< 0.05). The results were comparable to that produced by standard drug fluoxetine. CONCLUSION: Tapentadol have antidepressant activity which is comparable to fluoxetine. Further, studies are essential to prove the anti–depressant effect of Tapentadol in human.