Objective To investigate the relationship between zonula occludens- 1( ZO- 1) level and blood- brain barrier permeability in rats with hepatic encephalopathy( HE). Methods One hundred and eighty Sprague- Dawley rats were equally and randomly divided into control and HE( 4,8,and 12 h) groups of 45 animals each. Rats were given D- galactosamine( 400 mg / kg) and lipopolysaccharide( 100 μg/kg) by intraperitoneal injection to build an HE model. At 4,8,and 12 h after injection,blood ammonia concentration,Evans blue( EB) content,and brain water content were measured,and ZO- 1 mRNA level in the blood- brain barrier was assayed by real- time Q-PCR. Measurement data were analyzed using the least significant difference test( with homogeneous variances) and Dunnett T3 test( with heterogeneous variances). Results At 2 h after injection,the rats in the HE groups began to show HE symptoms. At 4 h after injection,the rats showed significant increases( P < 0. 001 for all) relative to the controls in blood ammonia concentration( 74. 27 ± 1. 77 μmol / L vs33. 85 ± 1. 50 μmol / L,),EB content( 4. 84 ± 0. 43 μg / g vs 3. 96 ± 0. 48 μg / g),and brain water content( 78. 63 ± 0. 46% vs 76. 07 ±0. 39%); the increases in the above three indices became more significant over time in the three HE groups( F = 5983. 36,111. 54,and737. 25,respectively; P < 0. 001 for all). In contrast,ZO- 1 mRNA expression in rat brain tissue began to decrease at 4 h after injection compared with the control( 1. 282 3 ± 0. 057 4 vs 1. 457 6 ± 0. 065 4,P < 0. 001); the decrease in the relative ZO- 1 mRNA expression level became more significant over time( F = 135. 38,P < 0. 001). Conclusion Blood- brain barrier permeability enhancement and brain edema in HE rats may be associated with the decrease in ZO- 1mRNA expression.