Micro–sized multivesicular liposomes were prepared, radiolabeled with ¹⁷⁷Lu, and tested in vitro and in vivo to evaluate the potential of ¹⁷⁷Lu–labeled micro liposomes in radiosynoviorthesis (RSO) therapy. A standard reverse–phase procedure of liposome preparation with a lipid mixture of DPPC: CHOL (80:20%) was used for the synthesis. TEM and fluorescence microscopy imaging were performed to determine the size, shape, and structure of the prepared liposomes. Both measurements are in good agreement while TEM micrographs additionally indicate to a large multivesicular inner structure of prepared liposomes. A simple and straightforward procedure was used for liposome radiolabeling with ¹⁷⁷Lu, a well–known and commonly used radionuclide in radiotherapy with favorable properties, that can be exploited in RSO therapy. Radiolabeled ¹⁷⁷Lu–liposomes were tested in vitro for stability and then injected into the knee joints of Wistar rats where liposome in vivo behavior was followed up to 30 days post injection. Results from both ex vivo biodistribution and in vivo imaging studies presented a high stability and retention (>94 %ID) of ¹⁷⁷Lu–micro liposomes in the synovial liquid for the entire observation period. Leakage of free ¹⁷⁷Lu or ¹⁷⁷Lu–liposomes from the synovial fluid has not been detected, indicating to a possible application of ¹⁷⁷Lu–liposomes in radiosynoviorthesis (RSO) therapy.