ABSTRACTAim: To determine the effect of gender difference in the antidepressant effect of fluoxetine (FLX) in mice in tail suspension test (TST).Methods: Swiss albino mice of either sex were used and the depression-like behavior was measured by TST.Results: The present study showed that there was a significant difference in the immobility period of male mice and female mice in TST. However, theantidepressant effect of FLX differs significantly in male mice and female mice in TST.Conclusion: It has been concluded that the antidepressant effect of FLX in TST was affected by the gender difference as suggested by the results ofthe present study.Keywords: Depression, Estrogen, Female, Fluoxetine, Mice, Serotonin.