Abstract: 4-AMinopyridine (4-AP)was shown to promote histamine release from isolatedrat peritoneal mast cells(PMC )in a dose-dependent manner.Potassium channel openers ,minoxidil(Min)200 mg·kg^-1 ig,diazoxide(Dia) 500 μmol·L^-1 in vitro and calcium antagonist nifedipine(Nif)125 mg· kg^-1 ig were found to inhibit 4-AP induced histamine release from rat PMC. Electronmicroscopy revealed that 4-AP caused partial degranulation of PMC and extrusion of granules and Min200 mg· kg^-1 ig retarded this phenomenon. These results provide evidence that potassium channelsare present in rat mast cell membrane and indicate that the mechanism of histamine release by 4-APmay be related to its potassium channel blocking effect. As a result of this effect, the calcium channelsopen and Ca²⁺ influx to the mast cells increases,thus eliciting histamine release. Potassium channelopeners seemed to be a new group of inhibitors of histamine release from mast cells.