Previous study has demonstrated that application of intermittent pneumatic compression on legs can cause vasodilation in distant skeletal muscle at the microcirculation level. This study evaluated the influence of inflation rate and peak-pressure duration on the vasodilatory effects of intermittent pneumatic compression. The cremaster muscles of 50 male rats were exposed and divided into five groups of 10 each. A specially designed intermittent pneumatic-compression device was applied in a medial-lateral fashion to both legs of all rats for 60 minutes, with an inflation rate and peak-pressure duration of 0.5 and 5 seconds, respectively, in group A, 5 and 0 seconds in group B, 5 and 5 seconds in group C, 10 and 0 seconds in group D, and 10 and 5 seconds in group E. Diameters of arterial segments were measured in vessels of three size categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed that the greatest increase in diameter was produced by intermittent pneumatic compression with the shortest inflation rate (0.5 seconds). A moderate increase resulted from compression with an inflation rate of 5 seconds, and no effective vasodilation occurred during compression with the longest inflation rate (10 seconds). When the groups with different inflation rates but the same peak-pressure duration were compared, there was a significant difference between any two groups among groups A, C, and E and between groups B and D. When the groups with different peak-pressure durations but the same inflation rate were compared, compression with a peak-pressure duration of 5 seconds caused a generally similar degree of diameter change as did compression without inflation at peak pressure. The findings suggest that inflation rate plays an important role in the modulation of distant microcirculation induced by intermittent pneumatic compression whereas peak-pressure duration does not significantly influence the vasodilatory effects of the compression. This may be due to the fact that rapid inflation produces a significant increase in shear stress on the vascular wall, which stimulates vascular endothelium to release nitric oxide, causing systemic vasodilation.