Bacterial persistence is a phenomenon in which heterogeneous gene expression in an isogenic cell population gives rise to a subgroup that can tolerate antibiotic treatment. This phenomenon was previously attributed to cell dormancy and stress response. Here we show by in vivo fluorescent imaging that enhanced efflux activities are widely observed in bacterial persisters under ß-lactam antibiotic treatment, which therefore suggests that the ability to actively pump antibiotics out is also a key mechanism producing persistence. Transcriptome sequencing revealed a number of multi-drug efflux associated genes have a higher expression level in persister cells. Unlike antibiotic resistance, where enhanced efflux activities are genetically coded, our observed enhanced efflux activity is transient and reversible. We further tested the combinational use of bacterial efflux inhibitors with antibiotics to reduce persisters and found potentiating effects. Our observation rectifies previous belief that biological activities are slowed down in persisters and provides a new therapeutic perspective.