Objective To evaluate the effectiveness of a major depression animal model for old man established with orchidectomized(ORX) and subsequently olfactory bulbectomized(OBX) rat. Methods Healthy Sprague-Dawley male adult rats were randomly assigned to six groups with ten rats in each group: intact, sham-operated, model, vehicle, fluoxetine plus testosterone propionate(Flu+ TP) and amitriptyline plus testosterone propionate(Ami+ TP) groups. ORX+ OBX rat model was established. Therapy of Flu or Ami (10 mg/kg, i.p.) combined with TP(25 mg/kg, s.c.) was administered. Behavioral changes of rats in each group were detected. Results Open field test: The number of rat crossing lattices in model((124.50±14.25)lattices) or vehicle group( 118.70±10.27) was significantly larger than those of intact(38.20±6.30), sham-operated(33.70±9.58), Flu+ TP (34.00±9.82) and Ami+ TP group (35.20±12.54). The rearing number of model or vehicle group was also significantly larger than those of intact, sham-operated, Flu+ TP and Ami+ TP group.Statistical differences in the above corresponding comparisons of open field test existed (P<0.01). Forced swimming test: The immobility time of model((131.70±32.44)s) or vehicle group ((135.10±34.01)s) was significantly longer than those of intact((66.60±12.06)s), sham-operated((62.00±13.38)s), Flu+ TP((59.60±8.89)s) and Ami+ TP group ((64.80±10.78)s). There were statistical differences in the above corresponding comparisons (P<0.01). Morris water maze test: The escape latency of model((62.00±26.05)s) or vehicle group ((60.52±27.00)s) was significantly longer than those of intact((24.19±9.12)s), sham-operated((21.06±8.13)s), Flu+ TP((22.88±8.01)s) and Ami+ TP group ((27.04±10.11)s); while the time rat swimming in the quadrant originally put a platform of model or vehicle group was significantly shorter than those of intact, sham-operated, Flu+ TP and Ami+ TP group. There were statistical differences in the above corresponding comparisons of Morris water maze test (P<0.01, P<0.05). Conclusion The above data demonstrates that ORX+ OBX rat model is both repeatability and reliability, and can be a major depression animal model of old man for future researches. Key words: Orchidectomy; Olfactory bulbectomy; Old man; Major depression; Androgen; Animal model