Abstract: OBJECTIVE To investigate the effects of extract of Periplaneta americana(APA) on nuclear transcription factor-κB(NF-κB) and macrophage migration inhibitory factor(MIF)'s expression in rats with portal hypertension. METHODS Sixty SD rats were divided into normal control group, model group, propranolol group, APA high, medium and low dose groups, 10 rats in each group. The model of rats with portal hypertension were prepared with CCl₄ and alcohol, 8 weeks of administration while modeling. The portal vein pressure of the rats were measured by direct manometric method, and the liver tissue morphology changes were observed. Besides, the expression level of NF-κB and MIF were detected by immunohistochemistry. RESULTS The portal vein pressure of model group was increased significantly compared with that of normal group(P<0.05), while such index in treatment groups(APA groups and propranolol group) was higher than that of normal group(P<0.05), but was lower significantly than that of model group(P<0.05). APA high and medium dose groups not only improved the pathology of damaged liver, but also decreased the expression of NF-κB and MIF in liver tissue. CONCLUSION APA can not only alleviate the hyperdynamic state of portal system, it is superior to the propranolol group, but also can decrease the expression of NF-κB and MIF, and finally improve the symptoms of portal hypertension. In addition to promoting angiogenesis, improving blood circulation and promoting tissue repair, the mechanism may be related to the inhibition of the expression of NF-κB and MIF in liver tissue.