Objective To investigate the effect of natural hirudin which is appl ied locally on vein congestion of random pattern skin flap in porcine models. Methods Three Guangxi Bama miniature pigs, including male and female aged 6-8 months and weighing 10-15 kg, were employed to establ ish animal model of vein congestive. Six dorsal random pattern skin flaps (three on each side) were prepared on each animal, 14 cm × 4 cm in size. According to the pharmacologic manipulations which were administered immediately and at 1, 2, and 3 days after operation respectively, the eighteen flaps were divided randomly into 3 groups (six in each group). In group A, isotonic Na chloride was locally appl ied as control group. In group B, 3 mL of 20 ATU natural hirudin was locally appl ied at each flap. In group C, 3 mL of 40 ATU natural hirudin was locally appl ied at each flap. Macroscopic observation (at 1 and 10 days postoperatively) and histological observation (at 1 and 7 days postoperatively) were made, the ratio of wet weight to dry weight of the congestive tissue (at 3 and 7 days postoperatively), the temperature of the surface of congestive flap (at 5 days postoperatively) and local blood flow of the flap (by Color Doppler Ultrasound at 7 days postoperatively) were measured. The survival rate of skin flaps was determined at 12 days postoperatively. Results Macroscopic observation showed that congestion of the flaps had no significance among three groups immediately after operation (P gt; 0.05); at 1 day postoperatively, the length of the congestion of the flap in group A (9.68 ± 0.43) cm was significantly longer than that in group B (6.81 ± 0.53) cm and group C (8.51 ± 0.64) cm (P lt; 0.05), while there was no significant difference between group B and group C (P gt; 0.05); at 10 days postoperatively, the necrosis at the distal end of flap in group A and group C were significantly longer than that in group B (P lt; 0.05), while there was no significant difference between group A and group C (P gt; 0.05). The histological observation revealed that the degree of erythrocyte agglutination in dermis capillary and veinule in group A was more serious than that of group B at 1 day postoperatively, and there was l ittle collagen and granulation tissue in group A when compared with group B at 7 days postoperatively. The ratio of wet weight to dry weight: at 3 days postoperatively, the value in group A (3.94 ± 0.14) was significantly higher than that of group B (3.43 ± 0.14) and group C (3.60 ± 0.19) (P lt; 0.05), and there was no significant difference between group B and group C (P gt; 0.05); at 7 days postoperatively, the value in group A (3.61 ± 0.11) was significantly higher than that of group B (3.08 ± 0.13) and group C (3.34 ± 0.21) (P lt; 0.05), and there was no significant difference between group B and group C (P gt; 0.05). The surface temperature of the congestive flap was (36.64 ± 0.70)℃ in group A, (38.61 ± 0.42)℃ in group B and (37.50 ± 0.46)℃ in group C at 5 days postoperatively; showing significant difference between group A and groups B, C (P lt; 0.05), and no significant difference between group B and group C (P gt; 0.05). The Color Doppler Ultrasound showed that the image of blood flow was very l ittle in group A, the image of venous return and perforator artery could be seen in group B and the image of arterial blood flow could be detected in group C. The survival rate of skin flaps was 45% ± 7% in group A, 67% ± 4% in group B and 52% ± 4% in group C at 12 days postoperatively; showing statistically significant difference between groups B, C and group A (P lt; 0.05), but no statistically significant difference between group B and group C (P gt; 0.05). Conclusion Local appl ication of natural hirudin can significantly improve the congestion of random pattern skin flap in a porcine model.