Clonidine at a dose of 0.00625–0.025 mg/kg (po) inhibited the gastric mucosal lesions induced by indomethacin, acidified aspirin, naproxen and piroxicam. The gastroprotective effect was reversed by the $$\alpha _{2^ - } ADRENOCEPTORS$$ antagonist yohimbine (5 mg/kg sc) and by the highly selective $$\alpha _{2^ - } andrenoceptor$$ antagonist berbane derivative, Ch-38083 (3.5 mg/kg sc). Clonidine also decreased the gastric acid secretion in pylorus-ligated rats at a dose of 0.2 mg/kg (given intraduodenally) but not at gastroprotective doses (0.00625–0.025 mg/kg). The antisecretory effect of clonidine was reversed by both yohimbine and Ch-38083. The $$\alpha _{2B^ - receptor} $$ antagonist prazosin (0.1 mg/kg sc) blocked the gastroprotective effect but failed to influence the antisecretory action of clonidine. Our data suggest that the $$\alpha _{2B^ - androceptor} $$ subtype might be involved in gastroprotection; however, the antisecretory effect is likely to be mediated by $$\alpha _{2A^ - like} $$ adrenoceptor subtype.