Nicotine (NC), the major alkaloid found in cigarettes and tobacco, is also found in some plants which are consumed daily by humans. The adverse and beneficial health effects of NC inhalation or ingestion are still controversial. Most studies on NC have focused on its effects on cardiovascular and nervous functions. However, literature is scanty on its dose- and sex-specific effects on renal function, the gap this study aims at bridging. A study of these effects in animals can point towards its sex-specific benefits or hazards in humans. Forty Wistar rats [20 males (M) and 20 females (F)], 120-150g, were housed in separate metabolic cages. Each sex was divided into 4 groups (n=5) thus: 1 [control (CN)] received 0.2mL/100g/day distilled water i.p. for 28 days, while 2, 3 and 4 received NC at 1, 2 and 4mg/kg/day i.p respectively for the same period. Twenty four hour urine samples were collected thereafter. The rats were sacrificed under ketamine anesthesia (10mg/kg i.m.). Their plasma and urine were assayed for creatinine (Jaffe, 1886), urea and uric acid (Randox kits), Na+ and K- (Flame Photometry) and HCO3- (titrimetry). Creatinine clearance (CCr) was calculated using standard formula. Their kidney sections were stained with H&E for histopathological examination. Values are Mean±S.E.M, compared by ANOVA and t-test. P<0.05 was considered significant. Urine Na+ (mMol/L) was significantly (SG) higher in M groups (GP) 2 and 3 [126.40±4.60 and 174.40±3.67 respectively (RS)] and F GP 3 (72.80±2.08) when compared with their respective CN (M=100.60±4.43; F=70.40±2.36). Urine Na+ in F GP 1, 2, 3 and 4 (70.40±2.36, 72.80±2.08, 92.80±5.16 and 76.60±6.17 RS) was SG lower than their M counterparts (CP) (100.60±4.43, 126.40±4.60, 174.40±3.67 and 120.80±7.52 RS). Plasma K+ (mMol/L) of GP 2, 3 and 4 (M=3.54±0.10, 3.72±0.05 and 3.32±0.08; F=3.26±0.07, 3.16±0.06 and 3.22±0.10 RS) was SG lower than their CN (4.20±0.06 and 3.68±0.12 RS). Plasma K+ in F groups 1, 2 and 3 (3.68±0.12, 3.26±0.07 and 3.16±0.06 RS) was SG lower than their M CP (4.20±0.06, 3.54±0.10 and 3.72±0.05 RS). CCr (x10-3mL/min) was SG higher in GP 2 and 3 (M=7.38±0.53 and 7.66±0.40; F=9.45±0.49 and 14.29±0.62 RS) than their CN (4.66±0.66 and 6.28±0.37 RS). CCr in F GP 2, 3 and 4 (9.45±0.49, 14.29±0.62 and 4.61±0.34 RS) was SG higher than their M CP (7.38±0.53, 7.66±0.40 and 3.41±0.38 RS). Photomicrographs revealed no appreciable distortion in the kidney histoarchitecture of all the rats. It was concluded that sub-chronic administration of low doses of NC alter the plasma and urine electrolyte balance and increase CCr of Wistar rats presumably by increasing their renal blood flow, an effect that was more pronounced in the females than the males.