Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract, Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the activities of CYP450 isozymes (CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) in rat hepatic microsomals were studied by using a UPLC-MS/MS (MRM) and cocktail probe substrates method.   The results showed that effects of six kinds of Chinese herb extracts on each CYP450 isozyme activity were inhibitory.  The IC₅₀ of Folium Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for 4.04 μg·mL⁻¹, which showed the highest inhibition; Trifolium pratense L. extract had strong inhibitory action to CYP2D, the IC₅₀ value was 5.73 μg·mL⁻¹; Folium Crataegi extract also had strong inhibitory action on CYP2E1, the IC₅₀ value was 10.91 μg·mL⁻¹.  Furthermore, the IC₅₀ of Folium Ginkgo extract for the inhibition of rat microsomal CYP3A, 2D, 2E1 activities were 45.12, 35.45 and 22.41 μg·mL⁻¹, respectively, and the IC₅₀ of Folium Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1 activity was 32.89 μg·mL⁻¹.  In addition, mechanism of inhibition experimental results showed that the inhibiting abilities of Folium Crataegi extract and Radix Puerariae extract on each CYP450 isozyme increased with the increasing of the preincubation time, therefore, the inhibitory effects were a mechanism-based inhibition.