OBJECTIVE: To observe the sex-specific effect of a high-salt diet in renal function, renal oxidative stress, and renal gene expression in Wistar rats. STUDY DESIGN: Wistar rats were sorted into 2 groups. Feeding of the normal (0.2%) or high (4%) NaCl diet started after weaning until 13 weeks of age. The parameters were then calculated by sex. RESULTS: The difference in blood pressure was more pronounced in male rats. Similarly, the kidney function markers, such as urinary protein, urinary albumin, and urinary L-FABP, and kidney oxidative stress marker, such as urinary thiobarbituric acid reactive substance level expressed as malondialdehyde, were lower in female than in male animals, proving the sex differences in the consequences of high salt intake. We tried to find some explanations of the observed sex-specific effects of a high-salt diet on renal parameters by analyzing renal gene expression. One thing that stood out was that some genes were regulated by sex differences due to the high-salt diet in Wistar rats. CONCLUSION: A higher blood pressure, worse kidney function, and higher renal oxidative stress had been observed in male rats than in female rats in reaction to high salt consumption. Sex-specific gene expression may explain these observations. (Anal Quant Cytopathol Histpathol 2021;43:761-771) © Science Printers and Publishers, Inc. © 2021 Science Printers and Publishers Inc.. All rights reserved.