To explore the association between computed tomography (CT)-measured sex-specific abdominal adipose tissue and the pathological grade of clear cell renal cell carcinoma (ccRCC).This retrospective study comprised 560 patients (394 males and 166 females) with pathologically proven ccRCC (467 low- and 93 high-grade). Abdominal CT images were used to assess the adipose tissue in the subcutaneous, visceral, and intermuscular regions. Subcutaneous fat index (SFI), visceral fat index (VFI), intermuscular fat index (IFI), total fat index (TFI), and relative visceral adipose tissue (rVAT) were calculated. Univariate and multivariate logistic regression analyses were performed according to sex to identify the associations between fat-related parameters and pathological grade.IFI was significantly higher in high-grade ccRCC patients than in low-grade patients for both men and women. For male patients with high-grade tumors, the SFI, VFI, TFI, and rVAT were significantly lower, but not for female patients. In both univariate and multivariate studies, the IFI continued to be a reliable and independent predictor of high-grade ccRCC, regardless of sex.Intermuscular fat index proved to be a valuable biomarker for the pathological grade of ccRCC and could be used as a reliable independent predictor of high-grade ccRCC for both males and females.Sex-specific fat adipose tissue can be used as a new biomarker to provide a new dimension for renal tumor-related research and may provide new perspectives for personalized tumor management decision-making approaches.• There are sex differences in distribution of subcutaneous fat and visceral fat. • The SFI, VFI, TFI, and rVAT were significantly lower in high-grade ccRCC male patients, but not for female patients. • Intermuscular fat index can be used as a reliable independent predictor of high-grade ccRCC for both males and females.© 2023. The Author(s).