In order to decipher the role of macrophages in vivo, it could be necessary to establish a model of macrophage depletion in the whole animal. One method to obtain animal models efficiently depleted in macrophages in different tissues (bone marrow, spleen, liver, lungs, brain, gut, peritoneal cavity, lymph nodes/vessels) and blood is the use of a clodronate-liposome solution. Here, we describe the protocol used to deplete efficiently macrophages in mouse bone marrow.