Pollution by the heavy metal lead (Pb) has become a threat to both aquaculture and food safety. In this study, the protective effects of a selected probiotic with good Pb binding capacity (Lactobacillus plantarum CCFM8661) against waterborne Pb exposure were evaluated in Nile tilapia (Oreochromis niloticus). One hundred and eighty fish were divided into four groups as control, Pb-only, Pb-plus-CCFM8661 and CCFM8661only. Fish were exposed to a dose of waterborne Pb level at 1 mg L À1 for 4 weeks, and the probiotic was administered at 10 8 CFU g À1 in fish diet twice daily. The results showed that dietary supplementation of CCFM8661 ameliorated the growth performance and prevented the death of Pb-exposed fish. Cotreatment with Pb and CCFM8661 also effectively decreased Pb accumulation in kidney, liver, gonad, brain, gills and muscle. Moreover, the administration of this probiotic alleviated Pb-induced oxidative stress, recovered digestive enzyme activities and blood daminolevulinic acid dehydratase activity, reversed alterations in innate immune status and decreased the frequencies of the nuclear abnormalities in peripheral blood erythrocytes of fish. These results suggested that CCFM8661 may be a novel dietary supplement against Pb toxicity at least in tilapia.