Abstract Background South-Asian immigrants to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) and increased adipose tissue insulin resistance (AT-IR), as compared to their Western counterparts. Fetuin-A is a hepatokine known to influence AT-IR. Aim Can plasma fetuin-A concentrations explain an ethnic difference in adipose tissue insulin resistance? Methods We performed a two-step euglycemic-hyperinsulinaemic clamp and measured plasma concentrations of fetuin-A and non-esterified fatty acids (NEFA), in 18 Pakistani and 21 Norwegians with T2DM (age 29–45y) in Norway. AT-IR was calculated as NEFA-suppression during the clamp. The adipokines/cytokines leptin, adiponectin, visfatin, PTX3, IL-1β, INF-γ, and IL-4 were measured in fasting plasma. Liver fat was estimated by CT-scans. Results Despite a lower BMI, Pakistani patients displayed higher AT-IR than Norwegians. NEFA-suppression during clamp was lower in Pakistani than Norwegians (mean=-20.6%, 95%CI=-40.8, -0.01 and p  = 0.046). Plasma fetuin-A concentration was higher in Pakistani than Norwegians (43.4 ng/mL12.7,74.0, p  = 0.007) and correlated negatively to %NEFA-suppression during clamp (rho=-0.39, p  = 0.039). Plasma fetuin-A concentration explained 22% of the ethnic difference in NEFA-suppression during the clamp. Pakistani patients exhibited higher plasma leptin and lower PTX3 levels than Norwegian, and plasma visfatin correlated positively to plasma fetuin-A levels in the Pakistani patients. We observed no correlation between plasma fetuin-A and liver fat, but fetuin-A correlated negatively with plasma IL-1β, INF-γ, and IL-4 concentrations. Plasma IL-4 concentration was lower in Pakistani than in Norwegian patients. Conclusion Fetuin-A may contribute to explain the discrepancy in T2DM prevalence between Pakistani and Norwegians patients by influencing AT-IR.