From puberty onwards, blood pressure (BP) is consistently higher in males when compared with females. The kidney plays a central role in the regulation of BP by regulating salt excretion. High salt diet (HSD) is implicated in the onset of hypertension. Generation of reactive oxygen species (ROS) is one of the mechanisms by which a HSD induces hypertension1, as HSD has been shown to drive production of ROS in the renal tissues2. Both oxidative stress3 and BP elevating effect of a HSD4 have been shown to exhibit sexual differences. Therefore, experiments were designed to assess the effect of gender on oxidative stress in uninephrectomised rats fed a HSD. Weanling Sprague-Dawley rats (90 – 100g) of both sexes were divided into 4 groups (n = 6) each. They were either sham operated or uninepherectomised under (90mg/kg bodyweight ketamine and 10mg/kg bodyweight xylazine i.p) anaesthesia and fed a normal 0.3% or high 4% NaCl salt diet for 10 weeks. Renal weight index and fluid balance were determined. BP was measured via carotid artery canulation under 25% Urethane and 1% alpha chloralose (5ml/kg bodyweight i.p) anaesthesia. Plasma concentration of nitrates was measured, lipid peroxidation (LP) and superoxide dismutase (SOD) activity was determined in the kidney homogenate. H&E histological staining of the kidney was also carried out. HSD increased fluid retention (ml) in sham male (16.83±2.07vs.11.34±1.91) and female (20.5±2.35vs.10.57±2.04) as well as in uninephrectomised male (22.17± 2.39vs.12.43± 1.84) and female (24.17±2.36vs.11.90±1.50) rats. However, gender has no effect on fluid balance. HSD elevated BP (mmHg) in sham male (121±2vs.101±4) and female (117±3vs.95±3) and also in uninephrectomised male (141±5vs.105±3) and female (131±5vs.104±3) rats. BP elevating effect of a HSD and uninephrectomy was higher in the males when compared with females (141±5vs.131±5). Reduction in the weight index of the remnant kidney was more in high salt fed males (0.27±0.015vs.0.30±0.013) and female (0.23±0.023vs.0.30±0.023) as well as in the females when compared with males (0.23±0.023vs.0.27±0.015). Plasma concentration of nitrates was reduced in uninephrectomised plus high salt diet groups: male (0.32±0.08vs.1.24±0.14) and female (0.75±0.07vs.1.60±0.23), and this reduction is more in the male (0.32±0.08vs.0.75±0.07). HSD increased LP (0.11±0.017vs.0.05±0.008) but reduced the SOD activity (2.04±0.26vs.4.02±0.24) in the kidney and this effect was higher in the males: LP (0.11±0.017vs.0.03±0.005). HSD aggravated to a greater extent Bowman’s capsule vacuolation and tubular atrophy observed in uninepherectomised groups in male when compared with female rats. Thus reduced NO production, increased oxidative stress and distortion of renal cytoarchitecture can contribute to the gender differences in the response to a HSD in uninephrectomised Sprague-Dawley rats.