The two-dimensional (2D) center-of-mass diffusion, D, of end-tethered poly(2-methyl-2-oxazoline) (PMOx) lipopolymer chains was studied in a Langmuir monolayer at the air-water interface using wide-field single molecule fluorescence microscopy. In this case, tethering and stabilization of hydrophilic PMOx chains at the air-water interface is accomplished via end-tethering to lipid molecules forming a hydrophobic anchor. To explore the influence of molecular weight, M-n, and surface concentration, c(s), on lateral mobility, two different PMOx chain lengths of n = 30 and 50 (n, number of monomer units) were analyzed over a wide range of c(s). Using multiparticle tracking analysis of TRITC-labeled PMOx lipopolymers, we found two regimes of lipopolymer lateral mobility. At low c(s), D is independent of surface concentration but increases with decreasing n. Here diffusion properties are well described by the Rouse model. In contrast, at more elevated c(s), the data do not follow Rouse scaling but are in good agreement with a free area-area model of diffusion. The current study provides for the first time experimental insight into the 2D center-of-mass diffusion of end-tethered polymers at the air-water interface. The obtained results will be of importance for the understanding of diffusion processes in polymer-tethered phospholipid bilayers mimicking biomembranes at low and high tethering concentrations.