Antibacterial agents based on nanoparticles (NPs) have many important applications, e.g., for the textile industry, surface disinfection, wound dressing, water treatment, and food preservation. Because of their prevalent use it is important to understand whether bacteria could develop resistance to such antibacterial NPs similarly to the resistance that bacteria are known to develop to antibiotics. Here, it is reported that Escherichia coli(E. coli) develops adaptive resistance to antibacterial ZnO NPs after several days' exposure to the NPs. But, in contrast to antibiotics‐resistance, the observed resistance to ZnO NPs is not stable—after several days without exposure to the NPs, the bacteria regain their sensitivity to the NPs' antibacterial properties. Based on the analyses it is suggested that the observed resistance is caused by changes in the shape of the bacteria and the expressions of membrane proteins. The findings provide insights into the response of bacteria to antibacterial NPs, which is important to elucidate for designing and evaluating the risk of applications based on antibacterial NPs.