To study antidepressant action of nicotine in animal model of depression. The animal model for depression, used was ‘Isolation induced hyperactivity in rats’. Doses given were vehicle 1ml/kg (intra-peritoneal), imipramine10mg/kg (intra-peritoneal), nicotine0.4mg/kg (subcutaneous), nicotine 0.2mg/kg (inhalational) Nicotine administered by subcutaneous route showed significant reduction in hyperactivity at 10 and 20 minutes when compared with that of vehicle (control) group. When it was compared with imipramine, it showed significant reduction in hyperactivity at 10 minutes. Nicotine administered by inhalation route showed significant reduction in hyperactivity at 10 min and at 30, 40 50 minutes when compared with that of control group. When compared with imipramine, it showed significant reduction in hyperactivity at 10 minutes and it showed comparable effect with that of imipramine at 30, 40, and 50 minutes. Nicotine administered by inhalation route produced significant reduction in hyperactivity at 10, 20, 30, 40,50minutes, when compared with that of nicotine administered by subcutaneous route. Combination with imipramine acute or chronic administration of nicotine by inhalational route showed significant reduction in hyperactivity, when compared with imipramine treated rats. Imipramine treated rats showed significant changes in behavior with persistent sniffing, intense biting and paw licking when it compared with vehicle treated rats. Behavioral changes in nicotine treated rats showed     significant change sat persistent sniffing, intense biting, and paw licking. Effects of nicotine with imipramine were studied on all the above parameters. Nicotine administered by subcutaneous and inhalation route showed significant antidepressantactivity. Key words: Behavioral Changes, Depression, Isolation-Induced Hyperactivity, Nicotine