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Antihypertensive drug therapies have demonstrated their capacity to modulate the inflammatory processes associated with hypertension, leading to improvements in disease progression. Given the prevalent use of polytherapy in treating most hypertensive patients, comprehending the time‐dependent effects of combination treatments on inflammation becomes imperative. In this study, spontaneously hypertensive rats (SHR) were divided into seven groups (n = 6): (i) SHR + vehicle, (ii) SHR + nebivolol, (iii) SHR + valsartan, (iv) SHR + lisinopril, (v) SHR + nebivolol–valsartan, (vi) SHR + nebivolol–lisinopril, and (vii) WKY + vehicle. Blood pressure was measured using the tail‐cuff method. Temporal alterations in inflammatory cytokines TNF‐α, IL‐6, and IL‐10 were assessed in serum through ELISA and mRNA expression in aortic tissue via qPCR after 1, 2, and 4 weeks of treatment with nebivolol, lisinopril, valsartan, and their respective combinations. Histological alterations in the aorta were assessed. The findings indicated that combined treatments reduced systolic and diastolic blood pressure in SHR. The nebivolol and lisinopril combination demonstrated a significant decrease in IL‐6 serum and mRNA expression at both 1 week and 4 weeks into the treatment. Additionally, TNF‐α mRNA expression also showed a reduction with this combination at the same time points. Particularly, nebivolol–valsartan significantly decreased TNF‐α serum and mRNA expression after one and four weeks of treatment. Furthermore, an elevation in serum IL‐10 levels was observed with both combination treatments starting from the second week onwards. This study provides compelling evidence that concurrent administration of nebivolol with lisinopril or valsartan exerts time‐dependent effects, reducing proinflammatory cytokines TNF‐α and IL‐6 while modifying IL‐10 levels in an experimental hypertensive model. [ABSTRACT FROM AUTHOR]