Objective: To investigate the changes of MAPK signal transduction in the syndrome of spleen-Yang deficiency. Methods: The model rats of spleen-Yang deficiency syndrome were established by the complex methods of improper diet and overstrain. The MAPK activity of the heart, the liver and the brain of the model rats were detected by the method of immunoprecipitation. Results: There was no change in the MAPK activity in the cytoplasm of the liver and brain tissue in the model rats of spleen-Yang deficiency syndrome. And the MAPK activity in the cytoplasm of the heart tissue was increased significantly (P<0.05). The herbs for replenishing spleen-Yang could increase (P<0.01) the MAPK activity of the cytoplasm of the liver tissue of the rats with spleen-Yang deficiency. But there was no change of MAPK activity in the other two tissues. Conclusion: The changes of the MAPK signal transduction in the syndrome of spleen-Yang deficiency are different among different tissues. The herbs for replenishing spleen-Yang have different effects on the MAPK activity in different tissues, which perhaps is one of the effective mechanism.