Ectopic fat deposition in skeletal muscle, termed myosteatosis, is a key factor in developing insulin resistance.This work aimed to evaluate the association between insulin resistance and myosteatosis in a large Asian population.A total of 18 251 participants who had abdominal computed tomography were included in this cross-sectional study. Patients were categorized into 4 groups according to quartiles of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and intermuscular adipose tissue (IMAT). The absolute values of TAMA, NAMA, LAMA, and IMAT and the ratios of NAMA/BMI, LAMA/BMI, and NAMA/TAMA were used as myosteatosis indices.The absolute values of TAMA, NAMA, LAMA, and IMAT appeared to increase with higher HOMA-IR levels, and LAMA/BMI showed a similar upward trend. Meanwhile, the NAMA/BMI and NAMA/TAMA index showed downward trends. As HOMA-IR levels increased, the odds ratios (ORs) of the highest quartile of NAMA/BMI and NAMA/TAMA index decreased and that of LAMA/BMI increased. Compared with the lowest HOMA-IR group, the adjusted ORs (95% CI) in the highest HOMA-IR group for the lowest NAMA/TAMA quartile were 0.414 (0.364-0.471) in men and 0.464 (0.384-0.562) in women. HOMA-IR showed a negative correlation with NAMA/BMI (r = -0.233 for men and r = -0.265 for women), and NAMA/TAMA index (r = -0.211 for men and r = -0.214 for women), and a positive correlation with LAMA/BMI (r = 0.160 for men and r = 0.119 for women); P was less than .001 for all.In this study, a higher HOMA-IR level was significantly associated with a high risk of myosteatosis.