It is unclear how α-adrenoceptors regulate, and whether imidazoline receptors are involved in the regulation of, nedullary respiratory rhythm generator (RRG).In rhythmically active medullary slices of newborn rats, this study investigated the effects moxonidine, an α-agonist with affinity to imidazoline Il receptors (Ⅲ-R), on RRG activity at network and synaptic levels.In anesthetized adult rats, the respiratory effects of intracisternal moxonidine were studied with plethysmography.Moxonidine caused significant frequency decreases in hypoglossal bursts and in the tonic excitatory inputs of RRG respiratory neurons in vitro.These effects were blocked partially by selective α2-antagonist SKF-86466 but completely by efaroxan, an %-antagonist with affinity to Ⅲ-R.Moxonidine decreased respiratory rate and induced periodical respiration in vivo, all of which were hardly sensitive to SKF-86466 but were prevented by efaroxan.Our results demonstrate that moxonidine inhibits the RRG and induces periodical respiration, which involves activation of both α2-adrenoceptors and Ⅲ-R.