Adult hippocampal neurogenesis has been demonstrated in several species and is regulated by both environmental and pharmacological stimuli. Repeated exposure to stress is known to induce the reduction of neurogenesis in the dentate gyrus (DG) of hippocampus. The present study aimed at determining whether the clinically effective antidepressant clomipramine may influence hippocampal proliferation and neurogenesis in adult rats subjected to the chronic unpredictable stress (CUS) procedure, a model of depression with predictive validity. Repeated administration of clomipramine (5 mg kg−1, intraperitoneal) for 3 weeks, starting 2 weeks after the beginning of the stress procedure, significantly reversed the reduction of behavior measured by open-field test and forced swimming test. Moreover, rats subjected to stress exhibited a 49.9% reduction of cell proliferation at the end of a 5-week stress period, an effect which was suppressed by clomipramine treatment. These results demonstrated that exposure to CUS, which results in a state of behavioral depression, decreases hippocampal cell proliferation and that these effects can be counteracted by chronic clomipramine treatment.