AIM: To study the effect of sphingosine 1-phosphate (S1P) on the increase in microvessel permeability induced by platelet activating factor (PAF). METHODS: The microvessel permeability was assessed by measuring hydraulic conductivity (Lp). To observe the effect of S1P and PAF on vascular endothelial-cadherin (VE-Cadherin), the microvessels were stained with immunofluorescence and examined by laser confocal microscopy. RESULTS: After giving PAF at concentration of 10 nmol/L, the Lp value of rat mesentery microvessel was significantly increased. However, after pretreatment with S1P, PAF did not give rise to a further significant change. The effect of PAF on microvascular endothelial cells could be seen: the formation of endothelial gap was induced, the microvascular fluorescence intensity significantly increased, a large number of fluorescent microspheres (FMs) distributed in the space among the endothelial cells. However, after pretreated with S1P, no obvious gap opening and the FMs accumulation were observed. Compared to normal control, no significant difference of the microvascular fluorescence intensity was found. CONCLUSION: PAF changes the structure of VE-Cadherin, leading to detachment of adherent junction, formation of intercellular gaps, which contributes to the increase in the permeability. S1P improves the increase in the microvessel permeability caused by PAF, which might be mediated by strengthening adherent junction and inhibiting the formation of endothelial gaps.