In conclusion, this study showed that icariin (50 mg/kg, 25 mg/kg) improved depression symptoms in the model rats via regulation of the PI3K-AKT pathway, boosting the expression of the regulatory methylene p85 and catalytic methylene p110 of PI3K, increasing the relative expression of p-AKT, and encouraging the expression of the anti-apoptosis factor Bcl-2, thus elevating the ratio of Bcl-2/Bax. This evidence concerns the gene AKT1 and major depressive disorder.