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In this study, we made an attempt to attenuate the dexamethasone induced hypertension through Biochanin-A (BCA) in experimental rats. Hypertension was induced in male albino Wistar rats by subcutaneous administration of dexamethasone (10μg/kg body weight). The rats were orally treated with BCA (10mg/kg body weight) once daily for 45 days and Nicorandil-treated group (6mg/kg body weight) included for comparison. We evaluated the changes in mean arterial pressure, heart rate, blood pressure, vascular function, oxidative stress markers, and gene expression of histone deacetylases (HDAC)-1, HDAC-2, and HDAC-8. Administration of BCA or Nicorandil showed noteworthy improvement in vascular function in experimental rats. Moreover, aortic eNOS expression was down regulated, and NADPH oxidase subunit p47phox was up regulated in hypertensive rats. The antihypertensive effects of BCA were connected with concomitant downregulation of p47phox expression and upregulation of eNOS expression. Dexamethasone exposure led to increased mRNA expression of HDACs expression in the kidneys and these were restored after BCA administration. In conclusion, our results are, therefore, BCA reduces hypertension in experimental rats and suggests that BCA might be used against the hypertension.