Novel pH-activatable fluorescent probes with various pK(a) values have been developed utilizing 4-nitro-benzo[1,2,5]oxadiazole derivatives (NBD) as fluorophores and piperazine moieties as proton receptors. Under acidic conditions, probe FoPz displayed significant fluorescent enhancement of about 30 fold with a pK(a) value of 5.70 and it responds rapidly and sensitively to intracellular pH distributions and cellular pH fluctuations.