Objective To study the therapeutic effect of Atractylodes macrocephala Koidz grown in Qimen (Qi Baizhu) on rat model with spleen qi deficiency. Methods The rat model with spleen qi deficiency was established with fatigue injury and restricted diet. The effects of different doses of A. macrocephala Koidz decoction from different areas on serum D-xylose content, gastrin, motilin, pepsin, trypsin, interleukin-6, growth inhibin, spleen and thymus index of spleen and thymus deficiency model rats were observed. Results Compared with control group, the weight of rats in the model group decreased significantly and the levels of D-xylose content, serum gastrin, pepsase, trypsin, spleen and thymus indexes of model rats were significantly lower than those in the control rats. But the levels of interleukin-6 and somatostatin were significantly elevated. After giving A. macrocephala Koidz decoction and Danfu Weierkang granule to the model group, the index of the administration group was opposite to that of the model group. Conclusion The changes of detection indexes in the model group treated with Qi Baizhu were more obvious. The above results indicated that the therapeutic effects of A. macrocephala Koidz from different origins were different. The experimental results showed that Qi Baizhu had therapeutic effect on rats with spleen qi deficiency.