Abstract Purpose To evaluate the effect of transarterial pulsed perfusion with 60°C saline on vascular permeability of tumor tissue, as well as its hepatic and renal toxicity, in a rabbit VX2 liver model. Materials and methods VX2 carcinomas were grown in rabbit livers, forty male New Zealand white tumor-bearing rabbits were randomly divided into four groups, followed by transarterial perfusion with 37°C saline 60ml (n=10) (control 1 group), transarterial pulsed perfusion with 37°C saline 60ml (n=10) (control 2 group), transarterial continuous perfusion with 60°C saline 60ml (n=10) (TCP group), transarterial pulsed perfusion with 60°C saline 60ml (n=10) (TPP group), the duration of time for tumor tissues in the range 43–45°C of the treated groups was measured with needle thermometer during perfusion. Vascular permeability was assessed using the extravasation of Evans blue (EB) dye in the tumor or normal liver tissues of the four groups separately, the tumor or normal liver tissues of the four groups were estimated by histopathologic examination, and hepatic and renal toxicity was evaluated by means of blood biochemical analysis. The vascular endothelial cells in the tumor were observed by transmission electron microscopy (TEM). Results The duration of time for tumor tissues in the range 43–45°C of TPP group showed significantly longer than that of TCP group (12.3±3.3min vs. 5.7±2.5min) (P<0.01). After perfusion, the EB content of tumor tissue in TPP group showed significantly higher than that in TCP group (15.21±0.94μg/100mg vs. 10.71±0.84μg/100mg) (P<0.01), and also showed significantly higher than that in the two control group (3.42±0.87μg/100mg, 3.57±0.64μg/100mg) (P<0.01). Blood chemical analysis indicating there was an increase (P<0.05) in the serum ALT, AST levels in the two heated perfusion groups at 1, 2, 4, 8h after infusion when compared to that in the two control group, but there was no significant difference in the serum ALT, AST levels among the four groups at 24h after perfusion (P>0.05), and there was no significant difference in the serum BUN, Cr levels among the four groups at 1, 2, 4, 8, 24h after perfusion. Observed by hematoxylin and eosin staining, there were no obvious signs of tissue destruction in liver tissue and tumor tissue. TEM indicating the endothelial cell gap was broadened and the endothelial cells’ microvillus was decreased after heated perfusion. Conclusions The vascular permeability of the rabbit VX2 tumor was significantly increased after transarterial pulsed perfusion with 60°C saline without significant increase in hepatic and renal toxicity.