Objective: Microbubble enhanced cavitation of high negative pressure pulsed ultrasound has been proved the ability of causing swollen hepatocytes and decreasing hepatic blood perfusion of rabbit. In this study, the relationship between microbubble enhanced cavitation and two kinds of water molecular transport related proteins-aquaporin 4 (AQP 4) and sodium potassium ATP enzyme (Na+-K+ ATPase)-were further investigated. Methods: Forty-one healthy New Zealand white rabbits were randomly divided into the control group (n=5) and three different irradiation time groups: group T1 (irradiation time=1 min, n=12), group T5 (irradiation time=5 min, n=12) and group T10 (irradiation time=10 min, n=12). Animals in group T1, group T5 and group T10 were treated with high peak negative pressure (P=2.0 MPa) ultrasound irradiation combined with microbubble. Liver tissue specimens were obtained after ultrasound irradiation. Liver tissue specimens were taken by laparotomy in the control group. Distribution of AQP 4 and Na+-K+ ATPase in each group was observed by immunohistochemical method, and expression of both protein was detected by western blot. Results: IHC results shows the number of AQP4 and Na+-K+ ATPase positive cells in treatment groups is much higher than that in control group. AQP4 protein expression in T1, T5 and T10 group is significantly higher than that in control group (P < 0.05). Comparison between groups shows that AQP4 protein expression in T5 group is significantly higher than that in T1 and T10 group (P < 0.05), while the difference between T1 and T10 group is not statistically significant. Na+-K+ ATPase in T5 group and T10 group is significantly higher than that in control group and T1 group (P < 0.05), while no significant difference shows between T1 group and control group (P > 0.05). Expression of Na+-K+ ATPase in T5 group is also significantly higher than that in T10 group (P < 0.05). Conclusion: Microbubble enhanced cavitation could cause increased expression of AQP 4 and Na+-K+ ATPase in normal rabbit liver while inducing liver edema. Ultrasonic irradiation time had an effect on the increase of protein expression.