The present study was undertaken to evaluate the comparative antidepressant activity of Ocimum sanctum (OS) and imipramine using animal models of depression. Imipramine (15 mg/kg/i.p) and herbal extract of OS (500 mg/kg/p.o) were subjected for its antidepressant activity using four different animal models of depression, viz: Forced Swimming Test (FST), Reserpine Reversal Test (RRT), Haloperidol-Induced Catalepsy (HIC), and Pentobarbitone Sleeping Time (PST) in male Wistar rats. The study after single administration of OS and imipramine revealed a statistically significant reduction in immobility time in FST, RRT, and protection against HIC, compared to control respectively. However there was no significant potentiation of PST. The antidepressant activity of OS was comparable to that of standard drug imipramine. The results of the present study indicate the potential for use of OS as an adjuvant in the treatment of depression.