Objective To investigate the expression of PI3K/AKT/mTOR signaling pathway in the diseased adrenal glands of patients with primary aldosteronism. Methods Forty-five patients with primary aldosteronism undergoing surgical treatment with complete clinical and pathological records were selected. The expression of pAKT, p-mTOR, p-S6 and vascular endothelial growth factor (VEGF) in the tissues of diseased adrenal glands was determined by immunohistochemical staining and Western blotting. The resected normal tissues of adrenal glands in surgical treatment in patients with renal cell carcinoma were served as control group (n=12). Results Patients with primary aldosteronism presented with polydipsia, polyuria, refractory hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. The expression of p-AKT, p-mTOR, p-S6 and VEGF in diseased adrenal glands in patients with primary aldosteronism was significantly higher than that in controls (P<0.05). The plasma aldosterone level was positively significantly related to the expression of p-AKT and p-mTOR in diseased adrenal glands in patients with primary aldosteronism (r²_p-AKT=0.356, P<0.01；r²_p-mTOR=0.295, P<0.05). Conclusion The expression of p-AKT, p-mTOR, p-S6 and VEGF of PI3K/AKT/mTOR signaling pathway in diseased adrenal tissues is significantly increased in patients with primary aldosteronism, which may participate in the development of primary aldosteronism.