To explore therapeutic mechanism of Huang Qi Si Jun Zi Tang, this paper studied the T4, ANP, cAMP, cGMP in a spleen －deficient mouse model induced by reserpine with radoinuclide tracer technique. The results: (1 ) The level of T4 in the serum of the spleendeficiency group was lower than that in the control group (P < 0. 025 ). Its level in the treated group was close to that in the control group. (2) The level of ANP in the plasma of spleen － deficiency group was significantly lower than that in the control group (P < 0. 001 ) and it was significantly higher in the treated group than in the splee－ deficiency group. (3 ) The levels of cAMP and cAMP/cGMP in the plasma of spleen－ deficiency group were significantly higher than those in the control group. The level of cAMP in the treated group was close to that in the control group. (4) The level of cGMP in the plasma of spleen－ deficiency group was significantly lower than that in the control group (P < 0. 001 ) and cGMP was higher in the treated group than that in spleendeficlenct group. (5) The body weight, weights of thymus, spleen, testis and uters in spleendeficient mice all increased after administration of the decoction.The results indicate that the Huang Qi Si Jun Zi Tang has good effects on spleen － deficient mice and can alleviated the spleen － deficiency syndrome. The therapeutic mechanism of Huang Qi Si Jun Zi Tang is related to its regulation of thyroid function and the levels of ANP cAMP cGMP and T4.