Abstract: Objective: To investigate the distribution of defibrase(DF) from Deinagkistrodon acutus venom in gastrointestinal tract and the change of plasma fibrinogen concentration in SD rats. Methods: After intragastric administration of DF from Deinagkistrodon acutus venom to SD rats, the signs of rats were observed and the acute toxicity of DF to rats was detected. Immunohistochemistry and enzyme-linked immunosorbent assay(ELISA) were used to detect the distribution of DF from Deinagkistrodon acutus venom in rat gastrointestinal tract and its dose-effect relationship and time-effect relationship with fibrinogen. Results: After intragastric administration of DF from Deinagkistrodon acutus venom(1,000 U/kg), there was no obvious toxic reaction in rats, and the oral toxicity of DF was very low. DF mainly existed in duodenum, stomach and jejunum after 3 h of intragastric DF. In the dose-effect relationship experiment, the fibrinogen level in rats after intragastric administration of DF(200 U/kg) was significantly lower than that in the control group(P<0.05); in the time-effect relationship experiment, the levels of fibrinogen on the 5th, 6th and 7th day after intragastric administration were significantly lower than those in the control group(P<0.05), and showed a time-and dose-dependent relationship. Conclusion: The DF from Deinagkistrodon acutus venom, when orally administrated, can be absorbed into the stomach, duodenum and jejunum through the gastrointestinal mucosa. Appropriate oral administration of DF can effectively reduce fibrinogen levels in rats, and continuous administration is more effective.