The adverse and beneficial health effects of nicotine (NIC), the major alkaloid found in cigarettes and tobacco, are controversial. Most studies on NIC have focused on its effects on cardiovascular and nervous functions. This study aimed at determining dose- and sex-specific effects of sub-acute (28 days) NIC administration on some indices of kidney function in Wistar rats. Forty rats (20 males and 20 females), 8-9 weeks old (each housed in separate metabolic cage), were used for this study such that graded doses of NIC (1, 2 and 4 mg/kg i.p. for 28 days) were administered to both sexes while each control received distilled water at 0.2 mL/100 g i.p. Blood was collected under ketamine anesthesia (10 mg/kg i.m) for analyses and results obtained were compared at p < 0.05. The result showed beneficial alterations in plasma and urine level of creatinine, urea and uric acid (p < 0.05) as well as plasma and urine electrolyte level (Na and K) in both sexes (p < 0.05). Also, there was significant improvement in creatinine clearance (p < 0.05) with no appreciable difference in their histological examination. Although these beneficial effects were more pronounced in the female than in the male (p < 0.05), administration at the highest dose showed potentially deleterious alterations from normal beneficial trend (p < 0.05) in both sexes. It was concluded that sub-acute administration of lower doses of NIC improves kidney function of Wistar rats; an effect that was more pronounced in the females than their male counterparts.