Calcitonin gene-related peptide is a potent intrinsic vasodilator, can induce prostacyclin release, and may inhibit membrane lipid peroxidation. This study examines the effect of calcitonin gene-related peptide on vessel diameters, capillary perfusion and contractile function of skeletal muscle after 4 or 5 hours of ischemia and during immediate reperfusion using the rat cremaster muscle model. Forty-two male rats were used; half of these received 0.2 ml of 10−7 M calcitonin gene-related peptide after 0, 15, and 30 minutes of reperfusion, while the other half received normal saline as a control. By means of intravital videomicroscopy, the diameters of 10 vessels per muscle were measured prior to ischemia and during reperfusion. The fluorescein filling area was determined at 15, 30, and 60 minutes of reperfusion. After 1 hour of reperfusion, muscle function was examined in vitro by quantifying the contractile response to electric field stimulation of the muscles in an organ bath system. There was a significant increase in the diameter of the arterioles, but not the small arteries, at every time point from 10 to 60 minutes of reperfusion. The fluorescein filling area was increased in treated muscles at every time point. Contractile function was not significantly preserved. In light of the ability of calcitonin gene-related peptide to relieve vasospasm and improve capillary perfusion, it may be useful in reducing reperfusion injury in the future.