Aim: Natriuretic peptides (NPs) have emerged as important regulators of lipid metabolism. Reduced levels of NPs are reported in obesity and in patients with type 2 diabetes (T2D). This NP deficiency may affect their ectopic fat distribution and lead to high risk of non-alcoholic fatty liver disease (NAFLD). Methods: In this cross-sectional study, the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and liver fat content was quantified using 1H-magnetic resonance spectroscopy in 120 patients with T2D. Results: NAFLD (defined as liver fat content ≥ 5.6%) was found in 57 (48%) of the T2D patients, who also had significantly lower NT-proBNP (P = 0.002) levels compared with patients without NAFLD, but did not differ as regards the presence of cardiovascular disease (CVD) or in kidney function. After adjusting for potential confounders (age, gender, HbA_1c, BMI, HOMA2-IR, CVD, eGFR), the odds ratio for the presence of NAFLD was increased by 2.9 (P = 0.048) for NT-proBNP levels < 45 ng/L. In a multivariable linear regression model, the relationship with NT-proBNP was further analyzed as a continuous variable, and was independently and inversely associated with increasing liver fat content after full adjustment (P = 0.031). Conclusion: Reduced plasma NT-proBNP levels are independently associated with high liver fat content in patients with T2D. The present study suggests that NP deficiency may play a role in the development of NAFLD in T2D.