Strongly red luminescent and water-soluble probes are very important for studying biological events and processes. Fluorescent nanoparticles (NPs) built from the aggregation-induced emission luminogen (AIEgen) and amphipathic polymeric matrixes have been considered as promising candidates for bioimaging. However, AIE NPs with long-wavelength absorption suitable for in vivo application are still scarce. In this work, three AIE-active red-emissive BODIPY derivatives with long-wavelength absorption were rationally designed and synthesized. Then three NPs based on these AIEgens exhibit bright red photoluminescence with high fluorescence quantum yield in aqueous media. These NPs uniformly dispersed in water and showed excellent stability and good biocompatibility. They can be readily internalized by HeLa cells, and the staining process is performed by simply shaking the culture with cells for just a few seconds at room temperature, which indicates an ultrafast and easy-to-operate staining protocol. More importantly, long-term tracing in living cells and mouse over 15 days is successfully achieved. The strong fluorescence signals, ultrafast staining procedure, and long-term tracing abilities indicate that these AIE NPs hold great potential for monitoring biological processes.