We present the photochemically induced olfactory bulbectomy (P-bulbectomy) as a novel method to ablate the olfactory bulb thus inducing an animal model of depression. The photosensitizer Rose Bengal was injected through the tail vein and then the cool halogen light illuminated the skull region overlying of the olfactory bulb for 10 min. Two weeks after surgery, P-bulbectomy had completely removed olfactory bulb uniformly in all animals. P-bulbectomy induced typical depression-related behaviors such as hyperactivity in the open field test and an enhancement of immobility time and in the forced swimming test. Depression-related neurohistological phenomenon was also seen; reduction of choline-acetyltransferase-positive cell numbers in the medial septum and a decline in cell proliferation in the dentate gyrus of hippocampus. This study shows that P-bulbectomy may be a convenient and reproducible experimental method to produce an animal model of depression.