To study the effect and molecular mechanisms of amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing on the treatment methods of renal failure and hypertension. A total of 60 cases of renal failure hypertension were randomly divided into the Control group and the Treatment group. The control group was treated with amlodipine besylate, while the treatment group was treated with amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing. A rat model of renal failure hypertension was established. Rats were divided into the sham group, model group, NC group (treated with amlodipine besylate) and treatment group (treated with amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing). Rats were given drugs at 10‑20 weeks of age to observe their general condition and detect changes of blood pressure, blood biochemical indices and urine index. The pathological changes of renal tissue were examined by hematoxylin and eosin staining, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)9 were detected by immunohistochemistry. Reverse transcription‑quantitative polymerase chain reaction was used to determine mRNA expression of phosphoinositide 3‑kinase (PI3K), protein kinase B (AKT) and endothelin (ET)‑1 and western blotting was used to detect the expression of phosphorylated (p)‑PI3K/PI3K, p‑AKT/AKT and p‑nuclear factor (NF)‑κB p65/NF‑κB p65 protein. Systolic and diastolic blood pressures in Treated group patients were significantly lower compared with in Control group patients. The systolic and diastolic blood pressure of rats were significantly decreased and blood urea nitrogen (BUN), carbapenem‑resistant Enterobacteriaceae (CRE), N‑acetyl‑β‑D‑glucosaminidase (NAG), urine protein (UP) and blood urea protein (BUP), contents were significantly decreased following amlodipine besylate treatment. The expression of VEGF and matrix metallopeptidase 9 protein were significantly decreased, but the expression of PI3K, AKT mRNA and p‑PI3K/PI3K, p‑AKT/AKT protein were significantly increased. ET‑1 mRNA and p‑NF‑κB p65/NF‑κB protein were significantly increased. The pathological alterations of renal tissue were improved and the pathological changes of glomerulus, tubule and interstitium were alleviated. Amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing can effectively reduce the systolic pressure and diastolic pressure of patients, and improve the symptoms and signs of patients, which may be associated with the regulation of the expression of PI3K/AKT pathway, so as to regulate the expression of BUN, CRE, UP, BUP and NAG.