Objectives: To investigate the enhancement of tumor perfusion using microbubbles and diagnostic ultrasound in patients with advanced pancreatic cancer. Methods: Twenty-one patients diagnosed with advanced pancreatic cancer, confirmed by histopathology or cytology, were enrolled. The tumor regions were treated with diagnostic ultrasound combined with microbubbles within 120 min after each clinical chemotherapy (albumin paclitaxel combined with gemcitabine, FOLFIRINOX regimen, or albumin paclitaxel combined with S-1), the tumor perfusion was dynamically observed before and after the treatment by contrast-enhanced ultrasound respectively., The time-intensity curve (TIC) of the treated area was analyzed by post-processing software. And the peak intensity (PI) and area under curve (AUC) can be calculated automatically. Results: Twenty-one pancreatic cancer patients treated by a total of 84 chemotherapy sessions, combining with ultrasound-generated microbubble cavitation. The PI of pancreatic cancer lesions increased from 109.19 ± 2.64 to 110.62 ± 2.70 after cavitation (P = 0.16), the AUC increased from 4752.76 ± 149.53 to 4863.67 ± 159.77 (P = 0.33). Neither of them was statistically significant. Conclusion: The sononeoperfusion effect excited by diagnostic ultrasound and microbubbles has the potential to increase blood perfusion of pancreatic cancer lesions in the clinic.