Objective To observe the changes of mRNA expression related to kidney yang deficiency and the ultrastructure of hypothalamus in Lewis rats, and further study the constitution of kidney yang deficiency in Lewis rats. Methods Ten 7-8-week old SPF male Lewis rats and twenty 7-8-week old SPF male Wistar rats were used in this study. The rats received subcutaneous injection of hydrocortisone to establish kidney yang deficiency model. The expressions of TNF-α, IFN-γ, IL-10, CRH, MR and GR mRNA in the hypothalamus of the two groups were detected and the ultrastructural changes of hypothalamus and adrenal gland were observed to compare the differences between the two groups, and to explore the mechanism of kidney yang deficiency constitution in the Lewis rats. Results Compared with the normal Wistar rats, the expressions of GR and IL-2 mRNA in the hypothalamus were significantly increased (P<0.01), while the expressions of CRH, TNF-α, IFN-γ and IL-10 mRNA were significantly decreased in the Lewis rats (P<0.01). The zona fasciculata of the adrenal cortex was slightly thinner, the mitochondria were slightly swollen and the amount of mitochondria was decreased. The nuclei of hypothalamic neurons were larger, and the mitochondria, neuron synapses and secretory vesicles in the presynaptic neurons were decreased. Conclusions There are abnormal expression of immune-related cytokines and CRH mRNA, and ultrastructural changes in the hypothalamus and adrenal gland of Lewis rats with kidney yang deficiency. Such changes may be related to the functional imbalance of the hypothalamus-pituitury-adrenal axis.