Leukocytes migrate rapidly through tissues without relying on integrin-mediated adhesion, a finding that challenges the traditional model of cell migration. This study demonstrates that integrins are not essential for three-dimensional migration in vivo, as leukocytes, including dendritic cells, can move through complex environments using actin-based protrusion and myosin II-dependent contraction. In contrast, integrins are crucial for crossing tissue barriers like the endothelial layer during extravasation. The study shows that leukocytes use a combination of actin network expansion for protrusion and squeezing contraction of the trailing edge to navigate through narrow spaces. This mechanism allows for rapid, flexible movement, distinct from the haptokinetic migration of other cells that rely on adhesion to the extracellular matrix. The findings suggest that leukocytes can move autonomously, adapting to various environments without the need for specific adhesive interactions. This model of migration, termed 'flowing and squeezing', enables immune cells to efficiently navigate through tissues, avoiding permanent remodeling of the extracellular environment. The study also highlights the functional dissociation between the leading and trailing edges of leukocytes, where protrusion and contraction operate independently, allowing for efficient locomotion in both two and three-dimensional environments. The results provide new insights into the mechanisms of leukocyte migration and have implications for understanding immune cell behavior in various physiological and pathological contexts.Leukocytes migrate rapidly through tissues without relying on integrin-mediated adhesion, a finding that challenges the traditional model of cell migration. This study demonstrates that integrins are not essential for three-dimensional migration in vivo, as leukocytes, including dendritic cells, can move through complex environments using actin-based protrusion and myosin II-dependent contraction. In contrast, integrins are crucial for crossing tissue barriers like the endothelial layer during extravasation. The study shows that leukocytes use a combination of actin network expansion for protrusion and squeezing contraction of the trailing edge to navigate through narrow spaces. This mechanism allows for rapid, flexible movement, distinct from the haptokinetic migration of other cells that rely on adhesion to the extracellular matrix. The findings suggest that leukocytes can move autonomously, adapting to various environments without the need for specific adhesive interactions. This model of migration, termed 'flowing and squeezing', enables immune cells to efficiently navigate through tissues, avoiding permanent remodeling of the extracellular environment. The study also highlights the functional dissociation between the leading and trailing edges of leukocytes, where protrusion and contraction operate independently, allowing for efficient locomotion in both two and three-dimensional environments. The results provide new insights into the mechanisms of leukocyte migration and have implications for understanding immune cell behavior in various physiological and pathological contexts.