In the main olfactory bulb recent history of activity input onto granule cells (GCs) can affect the strength of lateral inhibition, which functions to generate contrast enhancement.However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory inputs to mitral cells (MCs).Here we found that the repetitive stimulation of the two distinct excitatory inputs to GCs induced persistent modification in lateral inhibition with opposite directions.This bidirectional modification of inhibitory inputs differentially regulated subsequent synaptic plasticity of excitatory olfactory inputs to MCs, which was induced by repetitively pairing EPSPs with postsynaptic bursts.The metaplastic modification of spike timing-dependent plasticity was achieved by regulating the inter-spike-interval (ISI) of the postsynaptic bursts.This novel form of inhibition-dependent metaplasticity can contribute to the encoding or processing of olfactory information in the olfactory bulb.