Aim:The overexpression of the human tissue kallikrein (HK) gene can reduceblood pressure and ameliorate the secondary syndromes associated with hyper-tension in animal models.The current study was designed to investigate hy-potensive effect of intramuscular delivery of HK gene.Methods:We generatedan recombinant adeno-associated virus (rAAV) vector expressing human tissuekallikrein under the control of a cytomegalovirus promoter and administered therAAV-HK vector to a spontaneously hypertensive rat model at a dose of 1×10~(10)virons/rat through intramuscular injection.Results:A persistent,high-level ex-pression of HK post-gene delivery was confirmed by ELISA.The systolic bloodpressure in the rats receiving rAAV-LacZ and saline increased from 171.3 mmHg to182.3 mmHg 28 weeks’ post injection.In contrast,the delivery of the HK gene byAAV vectors attenuated the increase of the systolic blood pressure in the treatedgroup.The systolic blood pressure was only slightly lowered (from a level of 174mmHg to 170.5 mmHg) post-vector administration.The difference in blood pres-sure between the treated group and the control groups is statistically significantat 12.6 mmHg.The hypotensive effect of rAAV-HK persisted until the end of thetesting period.In addition,a significant amelioration of cardiovascularhypertrophy,renal injury,and collagen depositions in the rAAV-HK-treated ani-mals were also observed.Conclusion:All the effects are comparable with thoseof intravenous delivery.Therefore,the intramuscular administration of rAAV-HKmay be used in gene therapy for hypertension. Aim: The overexpression of the human tissue kallikrein (HK) gene can reduce blood pressure and ameliorate the secondary syndromes associated with hyper-tension in animal models. The current study was designed to investigate hy-potensive effect of intramuscular delivery of HK gene. Methods: We generated recombinant adeno-associated virus (rAAV) vector expressing human tissue kilallin under the control of a cytomegalovirus promoter and administered therAAV-HK vector to a spontaneously hypertensive rat model at a dose of 1 × 10 ~ (10) virons / rat through intramuscular injection Results: A persistent, high-level ex-pression of HK post-gene delivery was confirmed by ELISA. The systolic blood pressure in the rats receiving rAAV-LacZ and saline increased from 171.3 mmHg to 182.3 mmHg for 28 weeks’ post injection. contrast, the delivery of the HK gene by AAV vectors attenuated the increase of the systolic blood pressure in the treated group. the systolic blood pressure was only slightly (from a level of 174 mmHg to 170.5 mmHg) post-vector administration. The difference in blood pres-sure between the treated group and the control groups is statistically significant at 12.6 mmHg.The hypotensive effect of rAAV-HK persisted until the end of the testing period.In addition, a significant amelioration of cardiovascular hypeypertrophy, renal injury, and collagen deposition in the rAAV-HK-treated ani-mals were also observed. Conlusion: All the effects are comparable with those of intravenous delivery. Before, the intramuscular administration of rAAV-HK may be used in gene therapy for hypertension.