Objective To establish a cell bubble contact injury model for studying the pathogenesis of bubble-related diseases such as decompression sickness. Methods A cell bubble contact device was designed, including a bubble generating syringe, a cell culture dish, and a punching device. Bubbles with different diameters could be obtained by changing the diameter of the bubble generating syringe end, and the dose-effect relationship between cell damage, bubble diameter and contact time was observed by propidium iodide (PI) staining and cell counting kit 8 (CCK-8) cell viability test in primary cultured rat pulmonary microvascular endothelial cells (PMVECs), so as to establish a stable cell bubble contact injury model. Results The results of PI staining showed that there was no obvious damage to PMVECs after 1, 2, 3, or 4 h of 0.5 mm bubble contacting, while bubbles with diameters of 1.0, 1.5, and 2.0 mm increased the death of PMVECs after contacting 1, 2, 3, and 4 h; and the larger the bubble diameter and the longer the contact time, the more death of PMVECs were. Compared with the control group, CCK-8 cell viability test showed that bubbles with diameters of 1.0, 1.5, and 2.0 mm significantly decreased the viability of PMVECs after contacting 1, 2, 3, and 4 h (allP＜0.01). However, the cell damage of PMVECs was obvious only when the 2.0 mm diameter bubble was touched for more than 3 h. The cell viability was (84.27±1.35)% when the bubble with diameter 2.0 mm contacted the PMVECs for 3 h. Conclusion This study establishs a stable cell bubble contact injury model, which can be used to study bubble- related diseases such as decompression sickness. In addition, for PMVECs, 3 h of bubble contact with a diameter of 2.0 mm is the optimal condition for bubble-induced injuries.