Objective: The aim of this study is to evaluate the antidepressant activity of tapentadol using forced swimming test (FST) and tail suspension test (TST) experimental models.Methods: A total of 36 Swiss albino mice (18 for each experimental model) were divided into 3 groups of 6 animals each. In both the experimental models, Group I received normal saline -10 ml/kg (Control group), Groups II and III given tapentadol 20 mg/kg and tapentadol 40 mg/kg, respectively, for 7 days, intraperitoneally. On day 7, the drugs were given 40 minutes before conducting the experiment. The duration of immobility was noted and compared among all the 3 groups. The observations were analyzed using analysis of variance and Tukey's post-hoc test. Results:The duration of immobility was significantly decreased in both the experimental models. Tapentadol groups when compared to control group showed statistically significant values, and better results were obtained with tapentadol 20 mg/kg groups in both the models. The mean duration of Immobility was 34.67 seconds in FST model and 101.00 seconds in TST model when treated with tapentadol 20 mg/kg compared to 102.33 seconds in FST control and 141 seconds in TST control groups. FST model demonstrates greater antidepressant efficacy of tapentadol (p<0.00) than with TST model (p<0.04). Conclusion:Tapentadol showed significant antidepressant activity at the dose of 20 mg/kg. The results should be further confirmed by animal studies with different experimental models for the evaluation of depression and by human clinical studies, and if found effective, tapentadol can be preferred for patients with chronic pain, such as cancer pain.