The correlation between pulmonary endothelin receptors and alveolar-arterial oxygen gradient (A-aDO2) in rats with hepatopulmonary syndrome was investigated. Animals were divided into 2 groups: Sham-operated (Sham) group and common bile duct ligation (CBDL) group. Arterial blood gas was evaluated by a blood gas analyzer. The concentrations of ET-1 in blood and lung tissue sample were evaluated by radioimmunoassay. The distribution and expression of two kinds of subtype receptor of ET-1, ETRA and ETRB were examined by in situ hybridization. The results showed that the level of A-aDO2 was higher in CBDL group than that in Sham group (P＜0.05).The levels of plasma and pulmonary ET-1 in CBDL group were both higher than in Sham group (P ＜0.05). There was no significant difference in average A of ETRA between two groups by imaging analysis (0.21±0.06 vs 0.22±0.08, P＞0.05), while that of ETRB was higher in CBDL group than in Sham group (0. 58±0.16 vs 0.28±0.07, P＜0.05). The expression of ETRB in lung was positively correlated with A-aDO2 (P＜0.05). It was concluded that the widened A-aDO2 may be related with enhancement of the expression of ETRB in lung.