Sarcolemmal ATP-sensitive potassium (KATP) channels have been mentioned to participate in preconditioning protection. Since these channels are altered in diabetes, it would be possible that preconditioning does not develop in diabetic (D) hearts. The purpose of this study was to assess whether early (EP) and late (LP) ischemic preconditioning protect diabetic hearts against stunning in a conscious diabetic sheep model and whether diabetes might have altered KATP channel functioning. Sheep received alloxan monohydrate (1 g) and were ascribed to three experimental groups: control (DC, 12 min of ischemia (I) followed by 2 h of reperfusion (R)), early preconditioning (DEP, six 5 min I – 5 min R periods were performed before the 12 min I) and late preconditioning (DLP, same as DEP except that the preconditioning stimulus was performed 24 h before the 12 min I). Regional mechanics during reperfusion was evaluated as the percent recovery of wall thickening fraction (%WTH) expressed as percentage of basal values (100%) and KATP behaviour was indirectly assessed by monophasic action potential duration (MAPD) and sensitivity to glibenclamide blockade (0.1 and 0.4 mg/Kg). The results were compared to those obtained in normal (N) sheep. EP and LP protected against stunning in normal sheep (%WTH: NC = 63 ± 3.7, NLP = 80 ± 5**, NEP equals; 78 ± 3*, *p < 0.05="" and="" **p="">< 0.01="" against="" nc)="" whereas="" contrary="" results="" occurred="" in="" diabetic="" ones,="" where="" dlp="" (%wth="60" ±="" 4)="" afforded="" a="" similar="" recovery="" to="" dc="" (%wth="54" ±="" 5)="" and="" dep="" surprisingly="" worsened="" instead="" of="" improving="" mechanical="" function="" (%wth="38" ±="" 6,="" p="">< 0.01="" against="" dc).="" katp="" channel="" behaviour="" appeared="" altered="" in="" diabetic="" hearts="" as="" shown="" by="" mapd="" during="" ischemia="" in="" normal="" sheep="" (153="" ±="" 9="" msec)="" compared="" to="" diabetic="" ones="" (128="" ±="" 11="" msec,="" p="">< 0.05)="" and="" by="" the="" sensitivity="" to="" glibenclamide="" (while="" 0.4="" mg/kg="" blocked="" action="" potential="" shortening="" in="" normal="" and="" diabetic="" animals,="" 0.1="" mg/kg="" completely="" blocked="" katp="" in="" diabetic="" but="" not="" in="" normal="" hearts,="" p="" (="" 0.05).="" a="" sarcolemmal="" katp="" channel="" dysfunction="" might="" afford="" a="" primary="" approach="" to="" explain="" the="" absence="" of="" ischemic="" preconditioning="" protection="" against="" stunning="" in="" diabetic="">