In order to investigate the nature of Spleen deficiency and the mechanism of immunodepression due to Spleen deficiency and explore the pharmacological action of Chinese drugs of Yiqi Jianpi decoction (YQJP), the authors had established the rats model by administration Rhubarb. The preliminary results demonstrated that the symptoms manifested in rats were similar to those of Spleen deficiency syndrome. The changes of cyclic nucleotides in the spleen and plasma were unanimous. The cAMP level and the ratio of cAMP/cGMP decreased significantly while cGMP level increased significantly. Adenylate cyclase (AC) activity in the spleen reduced remarkably while cAMP-PDE activity had little changes. After the administration of YQJP, the symptoms of Spleen deficiency improved to normal extent. YQJP elevated the cAMP level, the ratio of cAMP/cGMP and AC activity while it lowered the cGMP level. The results showed that the changes of cyclic nucleotides level and the ratio of cAMP/cGMP were important targets of Spleen deficiency and that the action of YQJP followed the change of the ratio of cAMP/cGMP. The results of this study indicated that immunodepression of Rhubarb was due to depressing AC activity and reducing the ratio of cAMP/cGMP. The readjusting action of YQJP was concerned with AC system. This study supplied Spleen deficiency and YQJP with certain data in biochemical mechanism and pharmacological function.