Objectives: In this research, the effect of samul-tanggahyangbuja on depression and learning in ovariectomized rats subjected to repetitive stress were assessed. Samul-tanggahyangbuja is the prescription consisting of Samul-tang and Cyperi Rhizoma.Methods: Ovariectomized rats were repeatedly stressed over a 2-week period. After being orally medicated with samul-tanggahyangbuja (100 or 400 mg/kg), rats performed the Morris water maze test and forced swimming test, and social exploration was assessed in a behavior test. As well, sucrose intake was measured and measurements of blood serum corticosterone and the change of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in blood samples were made.Results: 1. In the Morris water maze test, rats medicated with 100 mg samul-tanggahyangbuja mastered the maze in a shorter time on the 4th day in comparison with the control group, while rats medicated with 400 mg samul-tanggahyangbuja mastered the maze more quickly (p<0.05 on the 3rd day ; p<0.01 on the 4th day, as compared to control).2. Immobility time in the forced swimming test was significantly decreased in rats receiving 400 mg samul-tanggahyangbuja compared with the control group (p<0.05).3. Sucrose intake and active social behavior of rats receiving 400 mg samultanggahyangbuja were markedly increased in comparison with the control group (p<0.01).4. Blood serum corticosterone measurements revealed decreased blood serum corticosterone level after medicating with samul-tanggahyangbuja. But it was not statistically significant.5. Treatment with either dose of samul-tanggahyangbuja significantly reduced IL-1β and TNF-α (p<0.05).Conclusions: These results suggest that samul-tanggahyangbuja possesses the anti-depressant and cognitive-enhancing activities related to menopause.