Objective: To discuss feasibility of permeation percutaneous administration of natural hirudin hydrogels and its toxic action on animal skin. Method: Natural hirudin hydrogels was prepared

improved Franz diffusion cells was adopted to make a permeability test

activity of natural hirudin was determined by Markwardt.Health Wistar rats were adopted to take an acute position skin test and single or multiple dose skin irritation test

health guinea pigs were used to make skin sensitization test. Result: Fibrinogen clotting times of experimental groups were delayed with P<0.05

it reached the maximum of (85.4±1.454) s at 3 h

while the control group had no significant delay;High-dose of natural hirudin hydrogels in short-term had no toxicity for skin

and no irritation for intact skin and broken skin of Wistar rats

no sensitization for intact skin of guines pigs. Conclusion: Natural hirudin could penetrate into intact skin tissue

its gels was safety for skin topical administration of experimental animals.