Objective To explore the effect of ischemic preconditioning (IPC) and diazoxide pretreatment (DPC) on diabetes hearts and its possible mechanism.Methods Using isolated working rat heart model, 40 SD rats with diabetes and 40 non-diabetic SD rats, were divided randomly into 5 groups.The control group (n=8) had a 120min perfusion without any intervension.The I/R group(n=8) had a 30-min equilibration period and a 30min ischemia and a 120min reperfusion.The IPC group(n=8) had a 10min equilibration, then was elicited by two cycles of 5min of ischemia interspersed with 5min reperfusion prior to 30min ischemia and a 120min reperfusion.The DPC group(n=8) had a 10min equilibration and two cycles of 5min of 100μM diazoxide perfusion followed by a 5min drug-free period before the 30min ischemia and a 120min reperfusion.Thedimethyl sulfoxide (DMSO) group (n=8) were perfused with the same treatment as in the DPC group,except that diazoxide was replaced with DMSO.The content of coronary outflow of creatine kinase (CK) in liquid changes, malondialdehyde (MDA) content and superoxide dismutase (SOD) changes of cGMP, NO, NOS content were detected.70nm ultrathin sections were made and the mitochondria under each specimen was evaluated according to Flameng score.Results CK activity of each group before ischemia content showed no significant difference (P>0.05).The content of CK was decreased in the non-diabetic group of IPC group and DPC group (P<0.01), while there were no significantly decreased in diabetic group (P>0.05).The MDA content in non-diabetic rats in IPC group and DPC group were significantly more than the I/R group (P<0.01), but there were no difference in the diabetic group (P>0.05).The content of SOD was higher than that in group I/R in non-diabetic rats in IPC group and DPC group (P<0.01), while in the diabetic group no statistical differences (P>0.05).Changes of myocardial NO, cGMP, and NOS content in non-diabetic group of IPC group and DPC group compared with I/R group increased significantly (P<0.01), while in the diabetic group, showed no significant difference (P>0.05).Flameng scores were compared between groups in the diabetic group, the difference was not statistically significant (P>0.05).Conclusion IPC and DPC have obvious protective effects on non-diabetic hearts, and the content of NO, cGMP and NOS were highly expressed.Diabetes could inhibit the effect of IPC and DPC, which may be related with theinhibiting of NO signal pathway in diabetic hearts.