Objective To explore the evaluation effect of contrast-enhanced ultrasound (CEUS) time-intensity curves (TIC) on angiogenesis of esophageal transplanted tumor in nude mice. Methods A total of 18 nude mice were selected and given subcutaneous injection of human esophageal cancer cell lines to construct models of esophageal transplanted tumor. At 4, 6 and 8 weeks after transplantation, 6 nude mice were selected for TIC analysis in region of interest (ROI) by CEUS. Quantitative parameters of CEUS TIC and imaging characteristics in esophageal transplanted tumor were compared after transplantation. The pathological changes of transplanted tumors were observed by hematoxylin-eosin (HE) staining, the expression of vascular endothelial growth factor (VEGF) protein and microvascular density (MVD) were analyzed by immunohistochemistry. The correlation between quantitative parameters of CEUS TIC and MVD, VEGF was analyzed by Pearson correlation analysis. Results Compared with those at 4 weeks after transplantation, peak intensity (PI), area wash in (AWI) and area wash out (AWO) were increased at 6 and 8 weeks after transplantation (P<0.05). Compared with those at 6 weeks after transplantation, PI and AWO were increased at 8 weeks after transplantation (P<0.05). At 4 weeks after transplantation, routine two-dimensional gray scale ultrasound showed that there were ellipsoid-like hypoechoic lumps with clear boundary and uneven internal echo. Color Doppler flow imaging showed that there were a few of blood flow signals in and around transplanted tumors of nude mice. At 6 weeks after transplantation, there was uneven and enhanced perfusion in transplanted tumors, and there were perfusion defects at 8 weeks after transplantation. The results of HE staining showed that at 4 weeks of transplantation, there was keratin pearl in transplanted tumors and intercellular bridge in cells. With time, keratin pearl and intercellular bridge were gradually decreased. Compared with that at 4 weeks after transplantation, MVD was increased at 6 and 8 weeks after transplantation (P<0.05), and expression of VEGF protein was increased at 8 weeks after transplantation (P<0.05). Pearson analysis showed that VEGF protein and MVD were positively correlated with PI, AWI and AWO (P<0.001). Conclusion CEUS TIC analysis can effectively evaluate the angiogenesis of human esophageal transplanted tumors in nude mice.