The aim of this study was to determine whether the length of ischemia in skeletal muscle influences the return of normal microvascular permeability during reperfusion in addition to influencing the size of the initial changes. In anesthetized rabbits, the transvascular clearance of labeled albumin was measured in the gastrocnemius and soleus muscles during the first, second, third, or fourth hour of reperfusion after 1, 2, 3, or 4 h of ischemia. The size of the increases in albumin clearance, tissue water, and myeloperoxidase activity during the first hour of reperfusion was dependent on the length of ischemia. The return of the albumin clearance to control values during the fourth hour of reperfusion was independent of the length of ischemia. Tissue water, extravascular mass of native albumin, and myeloperoxidase activity remained elevated during the 4 h of reperfusion. After 4 h of ischemia, the solvent-drag reflection coefficient for albumin was significantly less than control during the first hour of reperfusion. The value during the fourth hour of reperfusion was not significantly different from control. These results suggest that the inflammatory mediators producing a change in permeability are washed out of the microvasculature during the first few hours of reperfusion.