Abstract: This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyang deficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control (P<0.01), but dextromethorphan, omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the rat model.