Many studies suggest the dominant role of the inflammatory cytokine, tumor necrosis factor alpha (TNF-α) in the prognosis of hypertension and end stage renal disease (ESRD). The objective of this study was to investigate the effects of TNF-α inhibition on renal functions in Nω-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats and the potential underlying mechanisms. Four groups of rats were used in the study for 3 weeks period; normal control group, TNF- α inhibitor (etanercept) group, L-NAME-induced hypertensive group and L-NAME + etanercept group. L-NAME group showed elevated systolic and diastolic blood pressure, plasma urea, creatinine, plasma renin activity, angiotensin II, kidney tissue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, TNF- α and malondialdehyde (MDA) together with decreased creatinine clearance rate and renal antioxidants. Treatment with etanercept affords antihypertensive effect and ameliorates L-NAME induced renal impairment by improving renin–angiotensin system (RAS) and NADPH oxidase as well as by attenuating oxidative stress.