Abstract Disclosure: K. Han: None. K. Min: None. Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), significantly accelerating hepatic steatosis in animal study. Recently, the concept of a liver-spleen axis has been proposed in nonalcoholic fatty liver disease. The purpose of this study was to investigate change of the liver Hounsfield Units (HU), reflecting the hepatic steatosis, and its relation to spleen HU, central, or peripheral and ectopic adipose tissue during weight reduction in type 2 diabetes. Total 187 women with type 2 diabetes were educated on lifestyle modification. We assessed liver Hounsfield Units(HU) and spleen HU with total abdominal fat(ATAF) , visceral adipose tissue (AVAT), subcutaneous adipose tissue(ASAT) at mid-abdomen level, and total adipose tissue (TTAT)and intramuscular adipose tissue(TIMAT) at midthigh level using nonenhanced computed tomography, at baseline and 12 weeks. We investigated whether changes in liver HD were related to fat in other regions, serum triglycerides, free fatty acids, and adiponectin-leptin ratio (ALR). The participants’ age was 55.2±7.3 years, BMI was 27.3±2.7 kg/m2, Body Weight (BW) 66.8±6.9kg). Baseline liver HU was 54.7±11.5, and spleen HU was 48.5±8.5. At 12 weeks, BW lost 2.4±2.2kg. Liver HU changed with spleen HU (r=0.357, p<0.001, ATAT(r=-0.343, p<0.0001), AVAT (r=0.220, p=.011), ASAT(r=-0.339, p<0.001) and adiponectin-leptin ratio (ALR) (r=-0.174, p=0.047), but no significant relations with TTAT, TIMAT, triglyceride, and free fatty acid. Linear regression analysis showed the best model for change of liver HU (Model R2=0.209, p<0.001) was as follows: Change of Liver HU=0.534 +0.038* change of spleen HU - 0.290* change of ATAF. Higher spleen HU (p<0.001) and lower abdominal fat (p<0.001) predicted higher liver HU (less steatosis). These results suggested that the liver might be metabolically linked to the spleen in hepatic steatosis of type 2 Diabetes. Presentation: 6/2/2024